X-17725820-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 96632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-17725820-C-T is described in Lovd as [Benign]. Variant chrX-17725820-C-T is described in Lovd as [Likely_benign].

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.:

AF XY:

0.0526

AC XY:

1754

AN XY:

33372

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

GnomAD3 exomes

AF:

0.0253

AC:

4619

AN:

182822

Hom.:

196

AF XY:

0.0212

AC XY:

1427

AN XY:

67406

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 SAS exome

AF:

0.00881

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

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.00160

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00885

Gnomad4 FIN exome

AF:

0.00901

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0613

AC:

6819

AN:

111195

Hom.:

413

Cov.:

AF XY:

0.0524

AC XY:

1753

AN XY:

33435

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.0325

Gnomad4 ASJ

AF:

0.00378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00806

Gnomad4 FIN

AF:

0.00929

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.0685

Alfa

AF:

0.0187

Hom.:

876

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

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. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over