X-17375904-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001291867.2(NHS):​c.147C>T​(p.Val49Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

NHS
NM_001291867.2 synonymous

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0450

Publications

0 publications found
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 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

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP7
Synonymous conserved (PhyloP=-0.045 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NHSNM_001291867.2 linkc.147C>T p.Val49Val synonymous_variant Exon 1 of 9 ENST00000676302.1 NP_001278796.1 Q6T4R5-1
NHSNM_198270.4 linkc.147C>T p.Val49Val synonymous_variant Exon 1 of 8 NP_938011.1 Q6T4R5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NHSENST00000676302.1 linkc.147C>T p.Val49Val synonymous_variant Exon 1 of 9 NM_001291867.2 ENSP00000502262.1 Q6T4R5-1
NHSENST00000380060.7 linkc.147C>T p.Val49Val synonymous_variant Exon 1 of 8 1 ENSP00000369400.3 Q6T4R5-2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
984560
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
315912
African (AFR)
AF:
0.00
AC:
0
AN:
20609
American (AMR)
AF:
0.00
AC:
0
AN:
19591
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15904
East Asian (EAS)
AF:
0.00
AC:
0
AN:
22700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
42496
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
24783
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2666
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
794455
Other (OTH)
AF:
0.00
AC:
0
AN:
41356
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jun 01, 2015
Eurofins Ntd Llc (ga)
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
8.7
DANN
Benign
0.94
PhyloP100
-0.045
PromoterAI
-0.015
Neutral

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

Other links and lift over

dbSNP: rs794726961; hg19: chrX-17394027; API