chr21-44573880-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_198687.2(KRTAP10-4):āc.122G>Cā(p.Cys41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000067 ( 0 hom., cov: 47)
Exomes š: 0.0000041 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KRTAP10-4
NM_198687.2 missense
NM_198687.2 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 0.939
Genes affected
KRTAP10-4 (HGNC:20521): (keratin associated protein 10-4) This is an intronless gene located in a cluster of related genes on the q arm of chromosome 21. The proteins encoded by these genes form disulfide bonds with cysteine residues in hair keratins, thereby contributing to the structure and stability of hair fibers. [provided by RefSeq, Apr 2014]
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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRTAP10-4 | NM_198687.2 | c.122G>C | p.Cys41Ser | missense_variant | 1/1 | ENST00000400374.4 | NP_941960.2 | |
TSPEAR | NM_144991.3 | c.83-5875C>G | intron_variant | ENST00000323084.9 | NP_659428.2 | |||
TSPEAR | NM_001272037.2 | c.-122-5875C>G | intron_variant | NP_001258966.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRTAP10-4 | ENST00000400374.4 | c.122G>C | p.Cys41Ser | missense_variant | 1/1 | 6 | NM_198687.2 | ENSP00000383225.3 | ||
TSPEAR | ENST00000323084.9 | c.83-5875C>G | intron_variant | 1 | NM_144991.3 | ENSP00000321987.4 | ||||
TSPEAR | ENST00000642437.1 | n.*28-5875C>G | intron_variant | ENSP00000496535.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 149726Hom.: 0 Cov.: 47 FAILED QC
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GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245646Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133500
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000411 AC: 6AN: 1459218Hom.: 0 Cov.: 234 AF XY: 0.00000551 AC XY: 4AN XY: 725998
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000668 AC: 1AN: 149726Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0AN XY: 73212
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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 08, 2024 | The c.122G>C (p.C41S) alteration is located in exon 1 (coding exon 1) of the KRTAP10-4 gene. This alteration results from a G to C substitution at nucleotide position 122, causing the cysteine (C) at amino acid position 41 to be replaced by a serine (S). 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
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D;.
REVEL
Benign
Sift
Uncertain
.;D;.
Sift4G
Benign
.;T;.
Vest4
0.32
MutPred
0.52
.;Gain of glycosylation at C41 (P = 0.0017);.;
MVP
0.36
MPC
1.5
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at