Variant X-17376088-TCGGCGGCGG-TCGGCGGCGGCGG 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.348_350dup(p.Ala116dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,078,419 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 0 hom. 30 hem. )

Consequence

NHS
NM_001291867.2 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.485

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant X-17376088-T-TCGG is Benign according to our data. Variant chrX-17376088-T-TCGG is described in ClinVar as [Likely_benign]. Clinvar id is 588878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHS	NM_001291867.2 linkuse as main transcript	c.348_350dup	p.Ala116dup	inframe_insertion	1/9	ENST00000676302.1	NP_001278796.1
NHS	NM_198270.4 linkuse as main transcript	c.348_350dup	p.Ala116dup	inframe_insertion	1/8		NP_938011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1 linkuse as main transcript	c.348_350dup	p.Ala116dup	inframe_insertion	1/9		NM_001291867.2	ENSP00000502262	P4	Q6T4R5-1
NHS	ENST00000380060.7 linkuse as main transcript	c.348_350dup	p.Ala116dup	inframe_insertion	1/8	1		ENSP00000369400	A2	Q6T4R5-2

Frequencies

GnomAD3 genomes

AF:

0.000272

AC:

AN:

110366

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

33338

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00443

Gnomad AMR

AF:

0.000471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000875

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000152

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000246

AC:

AN:

32481

Hom.:

AF XY:

0.00

AC XY:

AN XY:

7751

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000793

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000759

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000114

AC:

110

AN:

968013

Hom.:

Cov.:

AF XY:

0.0000977

AC XY:

AN XY:

306963

show subpopulations

Gnomad4 AFR exome

AF:

0.000490

Gnomad4 AMR exome

AF:

0.000721

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00117

Gnomad4 SAS exome

AF:

0.000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000662

Gnomad4 OTH exome

AF:

0.0000737

GnomAD4 genome

AF:

0.000272

AC:

AN:

110406

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

33392

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.000470

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000879

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000152

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2017

This alteration is classified as likely 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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 23, 2022

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

NHS: BS2 -

NHS-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 2023

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

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