Variant rs797045741 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_001291867.2(NHS):c.310_345del(p.Pro104_Ala115del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,054,192 control chromosomes in the GnomAD database, including 7 homozygotes. There are 393 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., 66 hem., cov: 23)

Exomes 𝑓: 0.0012 ( 6 hom. 327 hem. )

Consequence

NHS
NM_001291867.2 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.11

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 -12 ACMG points.

BP6

Variant X-17376059-AGGCGGCGCCCGCAGCCGGCGAGGCGTCCTCGGCGGC-A is Benign according to our data. Variant chrX-17376059-AGGCGGCGCCCGCAGCCGGCGAGGCGTCCTCGGCGGC-A is described in ClinVar as [Benign]. Clinvar id is 211598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-17376059-AGGCGGCGCCCGCAGCCGGCGAGGCGTCCTCGGCGGC-A is described in Lovd as [Benign].

BS2

High Hemizygotes in GnomAd4 at 66 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHS	NM_001291867.2 linkuse as main transcript	c.310_345del	p.Pro104_Ala115del	inframe_deletion	1/9	ENST00000676302.1
NHS	NM_198270.4 linkuse as main transcript	c.310_345del	p.Pro104_Ala115del	inframe_deletion	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHS	ENST00000676302.1 linkuse as main transcript	c.310_345del	p.Pro104_Ala115del	inframe_deletion	1/9		NM_001291867.2	P4	Q6T4R5-1
NHS	ENST00000380060.7 linkuse as main transcript	c.310_345del	p.Pro104_Ala115del	inframe_deletion	1/8	1		A2	Q6T4R5-2

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

236

AN:

110635

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

AN XY:

33323

show subpopulations

Gnomad AFR

AF:

0.00501

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00273

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00349

Gnomad SAS

AF:

0.000752

Gnomad FIN

AF:

0.000345

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000628

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00540

AC:

112

AN:

20722

Hom.:

AF XY:

0.00711

AC XY:

AN XY:

5060

show subpopulations

Gnomad AFR exome

AF:

0.0370

Gnomad AMR exome

AF:

0.00588

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0400

Gnomad SAS exome

AF:

0.00533

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00265

Gnomad OTH exome

AF:

0.00453

GnomAD4 exome

AF:

0.00117

AC:

1108

AN:

943519

Hom.:

AF XY:

0.00110

AC XY:

327

AN XY:

298549

show subpopulations

Gnomad4 AFR exome

AF:

0.00745

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.000143

Gnomad4 EAS exome

AF:

0.00320

Gnomad4 SAS exome

AF:

0.00211

Gnomad4 FIN exome

AF:

0.000465

Gnomad4 NFE exome

AF:

0.000920

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00214

AC:

237

AN:

110673

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

AN XY:

33373

show subpopulations

Gnomad4 AFR

AF:

0.00506

Gnomad4 AMR

AF:

0.00263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00350

Gnomad4 SAS

AF:

0.000754

Gnomad4 FIN

AF:

0.000345

Gnomad4 NFE

AF:

0.000628

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00260

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 17, 2017

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 21, 2017

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

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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