chr21-44592331-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198688.3(KRTAP10-6):c.154T>C(p.Cys52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 8)
Consequence
KRTAP10-6
NM_198688.3 missense
NM_198688.3 missense
Scores
1
1
13
Clinical Significance
Conservation
PhyloP100: 0.354
Genes affected
KRTAP10-6 (HGNC:20523): (keratin associated protein 10-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36211893).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRTAP10-6 | NM_198688.3 | c.154T>C | p.Cys52Arg | missense_variant | 1/1 | ENST00000400368.1 | |
TSPEAR | NM_144991.3 | c.83-24326T>C | intron_variant | ENST00000323084.9 | |||
TSPEAR | NM_001272037.2 | c.-122-24326T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRTAP10-6 | ENST00000400368.1 | c.154T>C | p.Cys52Arg | missense_variant | 1/1 | NM_198688.3 | P1 | ||
TSPEAR | ENST00000323084.9 | c.83-24326T>C | intron_variant | 1 | NM_144991.3 | P1 | |||
TSPEAR | ENST00000642437.1 | c.*28-24326T>C | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 8
GnomAD3 genomes
Cov.:
8
GnomAD3 exomes AF: 0.00000420 AC: 1AN: 237932Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 129974
GnomAD3 exomes
AF:
AC:
1
AN:
237932
Hom.:
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0
AN XY:
129974
Gnomad AFR exome
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GnomAD4 exome Cov.: 23
GnomAD4 exome
Cov.:
23
GnomAD4 genome Cov.: 8
GnomAD4 genome
Cov.:
8
ExAC
AF:
AC:
3
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 10, 2023 | The c.154T>C (p.C52R) alteration is located in exon 1 (coding exon 1) of the KRTAP10-6 gene. This alteration results from a T to C substitution at nucleotide position 154, causing the cysteine (C) at amino acid position 52 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Vest4
MutPred
Gain of sheet (P = 0.0061);
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at