12-52567025-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_175053.4(KRT74):c.1534G>A(p.Asp512Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,604,024 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_175053.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT74 | NM_175053.4 | c.1534G>A | p.Asp512Asn | missense_variant | 9/9 | ENST00000305620.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT74 | ENST00000305620.3 | c.1534G>A | p.Asp512Asn | missense_variant | 9/9 | 1 | NM_175053.4 | P1 | |
KRT74 | ENST00000549343.5 | c.1576G>A | p.Asp526Asn | missense_variant | 10/10 | 5 | |||
KRT74 | ENST00000546384.1 | n.521G>A | non_coding_transcript_exon_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152058Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000186 AC: 27AN: 1451848Hom.: 1 Cov.: 30 AF XY: 0.0000166 AC XY: 12AN XY: 720894
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74398
ClinVar
Submissions by phenotype
KRT74-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 09, 2024 | The KRT74 c.1534G>A variant is predicted to result in the amino acid substitution p.Asp512Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at