rs139768159
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_014425.5(INVS):c.2803C>T(p.His935Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,614,000 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H935Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_014425.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INVS | NM_014425.5 | c.2803C>T | p.His935Tyr | missense_variant | 15/17 | ENST00000262457.7 | |
INVS | NM_001318381.2 | c.2515C>T | p.His839Tyr | missense_variant | 16/18 | ||
INVS | NM_001318382.2 | c.1825C>T | p.His609Tyr | missense_variant | 15/17 | ||
INVS | NR_134606.2 | n.2952C>T | non_coding_transcript_exon_variant | 15/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INVS | ENST00000262457.7 | c.2803C>T | p.His935Tyr | missense_variant | 15/17 | 1 | NM_014425.5 | A2 | |
INVS | ENST00000262456.6 | c.2293C>T | p.His765Tyr | missense_variant | 16/18 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00233 AC: 355AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00252 AC: 632AN: 251282Hom.: 2 AF XY: 0.00277 AC XY: 376AN XY: 135790
GnomAD4 exome AF: 0.00285 AC: 4167AN: 1461746Hom.: 14 Cov.: 32 AF XY: 0.00282 AC XY: 2049AN XY: 727172
GnomAD4 genome ? AF: 0.00233 AC: 355AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.00228 AC XY: 170AN XY: 74456
ClinVar
Submissions by phenotype
Infantile nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 12, 2016 | - - |
Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | INVS: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at