chrX-17687730-C-CT

Variant names:

• chrX-17687730-C-CT
• rs5901624
• NM_001291867.2:c.566-10dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_001291867.2(NHS):​c.566-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (38910 hom., 33276 hem., cov: 0)
  • Exomes 𝑓: 1.0 (367310 hom. 363551 hem.)
  • Failed GnomAD Quality Control
• Consequence: NHS NM_001291867.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.232
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Nance-Horan syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP6: Variant X-17687730-C-CT is Benign according to our data. Variant chrX-17687730-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 96644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2	c.566-10dupT		intron_variant	Intron 1 of 8	ENST00000676302.1	NP_001278796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1	c.566-10dupT		intron_variant	Intron 1 of 8		NM_001291867.2	ENSP00000502262.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 111054 AN: 111069 Hom.: 38915 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.999

GnomAD2 exomes AF: 1.00 AC: 183366 AN: 183374 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 1098182 AN: 1098197 Hom.: 367310 Cov.: 34 AF XY: 1.00 AC XY: 363551 AN XY: 363555

African (AFR) AF: 1.00 AC: 26396 AN: 26402

American (AMR) AF: 1.00 AC: 35204 AN: 35207

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 19386 AN: 19386

East Asian (EAS) AF: 1.00 AC: 30204 AN: 30204

South Asian (SAS) AF: 1.00 AC: 54147 AN: 54148

European-Finnish (FIN) AF: 1.00 AC: 40533 AN: 40533

Middle Eastern (MID) AF: 1.00 AC: 4136 AN: 4136

European-Non Finnish (NFE) AF: 1.00 AC: 842084 AN: 842087

Other (OTH) AF: 1.00 AC: 46092 AN: 46094

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 111107 AN: 111122 Hom.: 38910 Cov.: 0 AF XY: 1.00 AC XY: 33276 AN XY: 33280

African (AFR) AF: 1.00 AC: 30520 AN: 30531

American (AMR) AF: 1.00 AC: 10469 AN: 10472

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2641 AN: 2641

East Asian (EAS) AF: 1.00 AC: 3501 AN: 3501

South Asian (SAS) AF: 1.00 AC: 2567 AN: 2567

European-Finnish (FIN) AF: 1.00 AC: 5960 AN: 5960

Middle Eastern (MID) AF: 1.00 AC: 219 AN: 219

European-Non Finnish (NFE) AF: 1.00 AC: 53036 AN: 53036

Other (OTH) AF: 0.999 AC: 1511 AN: 1512

Alfa AF: 1.00 Hom.: 12697

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 2522 AN: 2522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jul 12, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 21, 2016

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nance-Horan syndrome Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 06, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cataract 40 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nance-Horan syndrome;C4049004:Cataract 40 Benign:1

Apr 25, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5901624; hg19: chrX-17705850;