X-17439178-A-T

Variant names:

• chrX-17439178-A-T
• rs6632979
• NM_001291867.2:c.565+62856A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001291867.2(NHS):​c.565+62856A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.93 (33834 hom., 28662 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: NHS NM_001291867.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2	c.565+62856A>T		intron_variant	Intron 1 of 8	ENST00000676302.1	NP_001278796.1
NHS	NM_198270.4	c.565+62856A>T		intron_variant	Intron 1 of 7		NP_938011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1	c.565+62856A>T		intron_variant	Intron 1 of 8		NM_001291867.2	ENSP00000502262.1
NHS	ENST00000380060.7	c.565+62856A>T		intron_variant	Intron 1 of 7	1		ENSP00000369400.3

Frequencies

GnomAD3 genomes AF: 0.932 AC: 100994 AN: 108363 Hom.: 33835 Cov.: 21

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.936

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.946

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.932 AC: 101047 AN: 108410 Hom.: 33834 Cov.: 21 AF XY: 0.933 AC XY: 28662 AN XY: 30736

African (AFR) AF: 0.985 AC: 29430 AN: 29874

American (AMR) AF: 0.945 AC: 9578 AN: 10139

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 2366 AN: 2609

East Asian (EAS) AF: 1.00 AC: 3354 AN: 3354

South Asian (SAS) AF: 0.991 AC: 2314 AN: 2335

European-Finnish (FIN) AF: 0.945 AC: 5110 AN: 5408

Middle Eastern (MID) AF: 0.939 AC: 200 AN: 213

European-Non Finnish (NFE) AF: 0.893 AC: 46700 AN: 52322

Other (OTH) AF: 0.947 AC: 1407 AN: 1486

Alfa AF: 0.921 Hom.: 8250

Bravo AF: 0.937

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6632979; hg19: chrX-17457301;