chr12-52567025-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
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 Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRT74 | ENST00000305620.3 | c.1534G>A | p.Asp512Asn | missense_variant | Exon 9 of 9 | 1 | NM_175053.4 | ENSP00000307240.2 | ||
KRT74 | ENST00000549343.5 | c.1576G>A | p.Asp526Asn | missense_variant | Exon 10 of 10 | 5 | ENSP00000447447.1 | |||
KRT74 | ENST00000546384.1 | n.521G>A | non_coding_transcript_exon_variant | Exon 3 of 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
not specified Uncertain:1
The c.1534G>A (p.D512N) alteration is located in exon 9 (coding exon 9) of the KRT74 gene. This alteration results from a G to A substitution at nucleotide position 1534, causing the aspartic acid (D) at amino acid position 512 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
KRT74-related disorder Uncertain:1
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