chr12-52567045-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_175053.4(KRT74):c.1514C>T(p.Ala505Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 1,598,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A505A) has been classified as Likely benign.
Frequency
Consequence
NM_175053.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT74 | NM_175053.4 | c.1514C>T | p.Ala505Val | missense_variant | 9/9 | ENST00000305620.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT74 | ENST00000305620.3 | c.1514C>T | p.Ala505Val | missense_variant | 9/9 | 1 | NM_175053.4 | P1 | |
KRT74 | ENST00000549343.5 | c.1556C>T | p.Ala519Val | missense_variant | 10/10 | 5 | |||
KRT74 | ENST00000546384.1 | n.501C>T | non_coding_transcript_exon_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000146 AC: 35AN: 240424Hom.: 0 AF XY: 0.000138 AC XY: 18AN XY: 130002
GnomAD4 exome AF: 0.0000650 AC: 94AN: 1446734Hom.: 0 Cov.: 30 AF XY: 0.0000669 AC XY: 48AN XY: 717628
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74406
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 07, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at