chr21-44591449-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_198688.3(KRTAP10-6):c.1036C>T(p.Arg346Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R346H) has been classified as Uncertain significance.
Frequency
Consequence
NM_198688.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRTAP10-6 | NM_198688.3 | c.1036C>T | p.Arg346Cys | missense_variant | 1/1 | ENST00000400368.1 | |
TSPEAR | NM_144991.3 | c.83-23444C>T | intron_variant | ENST00000323084.9 | |||
TSPEAR | NM_001272037.2 | c.-122-23444C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRTAP10-6 | ENST00000400368.1 | c.1036C>T | p.Arg346Cys | missense_variant | 1/1 | NM_198688.3 | P1 | ||
TSPEAR | ENST00000323084.9 | c.83-23444C>T | intron_variant | 1 | NM_144991.3 | P1 | |||
TSPEAR | ENST00000642437.1 | c.*28-23444C>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152180Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000236 AC: 59AN: 250490Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135518
GnomAD4 exome AF: 0.000144 AC: 210AN: 1461662Hom.: 0 Cov.: 34 AF XY: 0.000142 AC XY: 103AN XY: 727132
GnomAD4 genome ? AF: 0.000309 AC: 47AN: 152298Hom.: 0 Cov.: 34 AF XY: 0.000269 AC XY: 20AN XY: 74466
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.1036C>T (p.R346C) alteration is located in exon 1 (coding exon 1) of the KRTAP10-6 gene. This alteration results from a C to T substitution at nucleotide position 1036, causing the arginine (R) at amino acid position 346 to be replaced by a cysteine (C). 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