17-41583248-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000526.5(KRT14):c.1261G>A(p.Gly421Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. G421G) has been classified as Likely benign.
Frequency
Consequence
NM_000526.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRT14 | ENST00000167586.7 | c.1261G>A | p.Gly421Ser | missense_variant | Exon 6 of 8 | 1 | NM_000526.5 | ENSP00000167586.6 | ||
KRT14 | ENST00000441550.2 | n.208G>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 2 | |||||
KRT14 | ENST00000476662.1 | n.*1G>A | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251196Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135846
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461290Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726942
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74300
ClinVar
Submissions by phenotype
KRT14-related disorder Uncertain:1
The KRT14 c.1261G>A variant is predicted to result in the amino acid substitution p.Gly421Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0087% of alleles in individuals of Latino 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