12-52424684-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004693.3(KRT75):c.1489G>A(p.Gly497Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,614,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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_004693.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT75 | NM_004693.3 | c.1489G>A | p.Gly497Ser | missense_variant | 9/9 | ENST00000252245.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT75 | ENST00000252245.6 | c.1489G>A | p.Gly497Ser | missense_variant | 9/9 | 1 | NM_004693.3 | P1 | |
ENST00000548135.1 | n.292-3473C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251336Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135842
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461840Hom.: 0 Cov.: 33 AF XY: 0.0000481 AC XY: 35AN XY: 727216
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74488
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2023 | The c.1489G>A (p.G497S) alteration is located in exon 9 (coding exon 9) of the KRT75 gene. This alteration results from a G to A substitution at nucleotide position 1489, causing the glycine (G) at amino acid position 497 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at