rs10590816

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001291867.2(NHS):c.216_218delGCC(p.Pro73del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00632 in 1,071,997 control chromosomes in the GnomAD database, including 297 homozygotes. There are 1,744 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 153 hom., 958 hem., cov: 21)

Exomes 𝑓: 0.0033 ( 144 hom. 786 hem. )

Consequence

NHS
NM_001291867.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.20

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 -16 ACMG points.

BP6

Variant X-17375961-ACCG-A is Benign according to our data. Variant chrX-17375961-ACCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 96635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-17375961-ACCG-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2 link	c.216_218delGCC	p.Pro73del	disruptive_inframe_deletion	Exon 1 of 9	ENST00000676302.1	NP_001278796.1	Q6T4R5-1
NHS	NM_198270.4 link	c.216_218delGCC	p.Pro73del	disruptive_inframe_deletion	Exon 1 of 8		NP_938011.1	Q6T4R5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1 link	c.216_218delGCC	p.Pro73del	disruptive_inframe_deletion	Exon 1 of 9		NM_001291867.2	ENSP00000502262.1		Q6T4R5-1
NHS	ENST00000380060.7 link	c.216_218delGCC	p.Pro73del	disruptive_inframe_deletion	Exon 1 of 8	1		ENSP00000369400.3		Q6T4R5-2

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

3570

AN:

110092

Hom.:

153

Cov.:

AF XY:

0.0289

AC XY:

951

AN XY:

32952

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00437

Gnomad NFE

AF:

0.000343

Gnomad OTH

AF:

0.0246

GnomAD3 exomes

AF:

0.00377

AC:

186

AN:

49359

Hom.:

AF XY:

0.00276

AC XY:

AN XY:

17765

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.00690

Gnomad ASJ exome

AF:

0.000228

Gnomad EAS exome

AF:

0.00244

Gnomad SAS exome

AF:

0.000901

Gnomad FIN exome

AF:

0.000606

Gnomad NFE exome

AF:

0.000565

Gnomad OTH exome

AF:

0.00739

GnomAD4 exome

AF:

0.00333

AC:

3202

AN:

961861

Hom.:

144

AF XY:

0.00256

AC XY:

786

AN XY:

307081

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.00977

Gnomad4 ASJ exome

AF:

0.000125

Gnomad4 EAS exome

AF:

0.0000988

Gnomad4 SAS exome

AF:

0.000840

Gnomad4 FIN exome

AF:

0.000210

Gnomad4 NFE exome

AF:

0.000152

Gnomad4 OTH exome

AF:

0.00889

GnomAD4 genome

AF:

0.0325

AC:

3577

AN:

110136

Hom.:

153

Cov.:

AF XY:

0.0290

AC XY:

958

AN XY:

33006

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00113

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000344

Gnomad4 OTH

AF:

0.0243

Alfa

AF:

0.00694

Hom.:

Asia WGS

AF:

0.00592

AC:

AN:

2375

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 03, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 26, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 25, 2016

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 02, 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

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