21-44574068-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_198687.2(KRTAP10-4):c.310C>T(p.Pro104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000087 ( 0 hom., cov: 36)
Exomes 𝑓: 0.000010 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KRTAP10-4
NM_198687.2 missense
NM_198687.2 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: -0.462
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 Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.080840915).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRTAP10-4 | NM_198687.2 | c.310C>T | p.Pro104Ser | missense_variant | 1/1 | ENST00000400374.4 | |
TSPEAR | NM_144991.3 | c.83-6063G>A | intron_variant | ENST00000323084.9 | |||
TSPEAR | NM_001272037.2 | c.-122-6063G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRTAP10-4 | ENST00000400374.4 | c.310C>T | p.Pro104Ser | missense_variant | 1/1 | NM_198687.2 | P1 | ||
TSPEAR | ENST00000323084.9 | c.83-6063G>A | intron_variant | 1 | NM_144991.3 | P1 | |||
TSPEAR | ENST00000642437.1 | c.*28-6063G>A | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 13AN: 150002Hom.: 0 Cov.: 36 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000103 AC: 15AN: 1461218Hom.: 0 Cov.: 175 AF XY: 0.0000124 AC XY: 9AN XY: 726916
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000866 AC: 13AN: 150112Hom.: 0 Cov.: 36 AF XY: 0.000109 AC XY: 8AN XY: 73314
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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 | Jun 22, 2023 | The c.310C>T (p.P104S) alteration is located in exon 1 (coding exon 1) of the KRTAP10-4 gene. This alteration results from a C to T substitution at nucleotide position 310, causing the proline (P) at amino acid position 104 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
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
.;D
REVEL
Benign
Sift
Benign
.;T
Sift4G
Benign
.;T
Vest4
0.18
MVP
0.085
MPC
0.46
ClinPred
T
GERP RS
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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