rs373464879
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_001291867.2(NHS):c.2909C>T(p.Thr970Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,210,145 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T970T) has been classified as Benign.
Frequency
Consequence
NM_001291867.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHS | NM_001291867.2 | c.2909C>T | p.Thr970Met | missense_variant | 7/9 | ENST00000676302.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHS | ENST00000676302.1 | c.2909C>T | p.Thr970Met | missense_variant | 7/9 | NM_001291867.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000624 AC: 7AN: 112154Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34312
GnomAD3 exomes AF: 0.0000437 AC: 8AN: 183263Hom.: 0 AF XY: 0.0000738 AC XY: 5AN XY: 67753
GnomAD4 exome AF: 0.0000519 AC: 57AN: 1097991Hom.: 0 Cov.: 33 AF XY: 0.0000716 AC XY: 26AN XY: 363351
GnomAD4 genome ? AF: 0.0000624 AC: 7AN: 112154Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34312
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2014 | The p.T949M variant (also known as c.2846C>T), located in coding exon 6 of the NHS gene, results from a C to T substitution at nucleotide position 2846. The threonine at codon 949 is replaced by methionine, an amino acid with some similar properties. This variant was previously reported in the SNPDatabase as rs373464879. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele was absent out of 2443 total male alleles studied. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Nance-Horan syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at