rs147497359

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001291867.2(NHS):c.828G>A(p.Glu276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,207,953 control chromosomes in the GnomAD database, including 1 homozygotes. There are 91 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., 22 hem., cov: 21)

Exomes 𝑓: 0.00020 ( 1 hom. 69 hem. )

Consequence

NHS
NM_001291867.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.147

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant X-17692444-G-A is Benign according to our data. Variant chrX-17692444-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 196598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.147 with no splicing effect.

BS2

High Hemizygotes in GnomAd at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHS	NM_001291867.2 linkuse as main transcript	c.828G>A	p.Glu276=	synonymous_variant	3/9	ENST00000676302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHS	ENST00000676302.1 linkuse as main transcript	c.828G>A	p.Glu276=	synonymous_variant	3/9		NM_001291867.2	P4	Q6T4R5-1

Frequencies

GnomAD3 genomes

AF:

0.000865

AC:

AN:

109810

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

AN XY:

32060

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000390

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.000171

Gnomad OTH

AF:

0.00205

GnomAD3 exomes

AF:

0.000414

AC:

AN:

183444

Hom.:

AF XY:

0.000339

AC XY:

AN XY:

67880

show subpopulations

Gnomad AFR exome

AF:

0.00319

Gnomad AMR exome

AF:

0.000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.000882

GnomAD4 exome

AF:

0.000199

AC:

219

AN:

1098089

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

363477

show subpopulations

Gnomad4 AFR exome

AF:

0.00273

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000923

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.000412

GnomAD4 genome

AF:

0.000865

AC:

AN:

109864

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

32124

show subpopulations

Gnomad4 AFR

AF:

0.00252

Gnomad4 AMR

AF:

0.000389

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000171

Gnomad4 OTH

AF:

0.00203

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.00110

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 28, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 07, 2015	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2018

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 09, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

5.6

Dann

Benign

0.47

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