rs41304731

Positions:

chrX-17728035-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001291867.2(NHS):c.3929G>T(p.Gly1310Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,209,897 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 536 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., 32 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 0 hom. 504 hem. )

Consequence

NHS
NM_001291867.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.689

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.011122316).

BP6

Variant X-17728035-G-T is Benign according to our data. Variant chrX-17728035-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 96640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-17728035-G-T is described in Lovd as [Benign]. Variant chrX-17728035-G-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 32 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHS	NM_001291867.2 linkuse as main transcript	c.3929G>T	p.Gly1310Val	missense_variant	7/9	ENST00000676302.1	NP_001278796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1 linkuse as main transcript	c.3929G>T	p.Gly1310Val	missense_variant	7/9		NM_001291867.2	ENSP00000502262	P4	Q6T4R5-1

Frequencies

GnomAD3 genomes

AF:

0.000752

AC:

AN:

111672

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

AN XY:

33848

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00152

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.00120

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.000661

AC:

121

AN:

183187

Hom.:

AF XY:

0.000665

AC XY:

AN XY:

67667

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.000693

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.000663

GnomAD4 exome

AF:

0.00137

AC:

1501

AN:

1098172

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

504

AN XY:

363528

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.000596

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.000222

Gnomad4 NFE exome

AF:

0.00169

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000752

AC:

AN:

111725

Hom.:

Cov.:

AF XY:

0.000944

AC XY:

AN XY:

33911

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.00152

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00120

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.000981

Hom.:

Bravo

AF:

0.000669

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000601

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.00166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 09, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 25, 2016	- -

Nance-Horan syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

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

- -

NHS-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 11, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.6

DANN

Benign

0.095

DEOGEN2

Benign

0.0077

.;.;T;T

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.69

T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.070

N;N;.;.

REVEL

Benign

0.018

Sift

Benign

0.31

T;T;.;.

Sift4G

Benign

0.49

T;T;T;T

Vest4

0.035

MVP

0.068

MPC

0.43

ClinPred

0.0014

GERP RS

-5.1

gMVP

0.19

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