X-17725820-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001291867.2(NHS):c.1714C>T(p.Pro572Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0219 in 1,209,406 control chromosomes in the GnomAD database, including 888 homozygotes. There are 7,921 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 413 hom., 1753 hem., cov: 22)

Exomes 𝑓: 0.018 ( 475 hom. 6168 hem. )

Consequence

NHS
NM_001291867.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.86

Publications

5 publications found

Variant links:

Genes affected

NHS (HGNC:7820): (NHS actin remodeling regulator) This gene encodes a protein containing four conserved nuclear localization signals. The encoded protein functions in eye, tooth, craniofacial and brain development, and it can regulate actin remodeling and cell morphology. Mutations in this gene have been shown to cause Nance-Horan syndrome, and also X-linked cataract-40. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2014]

NHS Gene-Disease associations (from GenCC):

Nance-Horan syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NHS links:

ENSG00000309710 (HGNC:):

ENSG00000309710 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016627014).

BP6

Variant X-17725820-C-T is Benign according to our data. Variant chrX-17725820-C-T is described in ClinVar as Benign. ClinVar VariationId is 96632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2 link	c.1714C>T	p.Pro572Ser	missense_variant	Exon 7 of 9	ENST00000676302.1	NP_001278796.1	Q6T4R5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1 link	c.1714C>T	p.Pro572Ser	missense_variant	Exon 7 of 9		NM_001291867.2	ENSP00000502262.1		Q6T4R5-1

Frequencies

GnomAD3 genomes

AF:

0.0614

AC:

6822

AN:

111142

Hom.:

413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00294

Gnomad AMR

AF:

0.0326

Gnomad ASJ

AF:

0.00378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00803

Gnomad FIN

AF:

0.00929

Gnomad MID

AF:

0.0549

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.0694

GnomAD2 exomes

AF:

0.0253

AC:

4619

AN:

182822

AF XY:

0.0212

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.00227

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00889

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0179

AC:

19630

AN:

1098211

Hom.:

475

Cov.:

AF XY:

0.0170

AC XY:

6168

AN XY:

363565

show subpopulations

African (AFR)

AF:

0.190

AC:

5023

AN:

26401

American (AMR)

AF:

0.0163

AC:

575

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00160

AC:

AN:

19386

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30205

South Asian (SAS)

AF:

0.00885

AC:

479

AN:

54148

European-Finnish (FIN)

AF:

0.00901

AC:

365

AN:

40523

Middle Eastern (MID)

AF:

0.0580

AC:

240

AN:

4135

European-Non Finnish (NFE)

AF:

0.0139

AC:

11733

AN:

842114

Other (OTH)

AF:

0.0257

AC:

1183

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

902

1804

2705

3607

4509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

518

1036

1554

2072

2590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0613

AC:

6819

AN:

111195

Hom.:

413

Cov.:

AF XY:

0.0524

AC XY:

1753

AN XY:

33435

show subpopulations

African (AFR)

AF:

0.181

AC:

5499

AN:

30423

American (AMR)

AF:

0.0325

AC:

344

AN:

10573

Ashkenazi Jewish (ASJ)

AF:

0.00378

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3526

South Asian (SAS)

AF:

0.00806

AC:

AN:

2606

European-Finnish (FIN)

AF:

0.00929

AC:

AN:

6030

Middle Eastern (MID)

AF:

0.0556

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0146

AC:

772

AN:

52991

Other (OTH)

AF:

0.0685

AC:

103

AN:

1504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

207

414

622

829

1036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0329

Hom.:

2008

Bravo

AF:

0.0695

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0170

AC:

ESP6500AA

AF:

0.191

AC:

734

ESP6500EA

AF:

0.0149

AC:

100

ExAC

AF:

0.0286

AC:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 24, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 28, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27884173, 21559051) -

Inborn genetic diseases

Benign:1

Dec 13, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Nance-Horan syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;.;T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;D;D

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.2

PhyloP100

5.9

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.7

D;D;.;.

REVEL

Benign

0.25

Sift

Uncertain

0.0090

D;D;.;.

Sift4G

Uncertain

0.024

D;D;D;D

Vest4

0.46

MPC

0.45

ClinPred

0.018

GERP RS

5.9

gMVP

0.67

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over