chr21-44574039-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_198687.2(KRTAP10-4):c.281G>A(p.Ser94Asn) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 36)
Exomes 𝑓: 0.000023 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KRTAP10-4
NM_198687.2 missense
NM_198687.2 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: 4.97
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 -4 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.041315466).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRTAP10-4 | NM_198687.2 | c.281G>A | p.Ser94Asn | missense_variant | 1/1 | ENST00000400374.4 | NP_941960.2 | |
TSPEAR | NM_144991.3 | c.83-6034C>T | intron_variant | ENST00000323084.9 | NP_659428.2 | |||
TSPEAR | NM_001272037.2 | c.-122-6034C>T | intron_variant | NP_001258966.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRTAP10-4 | ENST00000400374.4 | c.281G>A | p.Ser94Asn | missense_variant | 1/1 | 6 | NM_198687.2 | ENSP00000383225.3 | ||
TSPEAR | ENST00000323084.9 | c.83-6034C>T | intron_variant | 1 | NM_144991.3 | ENSP00000321987.4 | ||||
TSPEAR | ENST00000642437.1 | n.*28-6034C>T | intron_variant | ENSP00000496535.1 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 151802Hom.: 0 Cov.: 36
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GnomAD3 exomes AF: 0.0000621 AC: 15AN: 241440Hom.: 0 AF XY: 0.0000606 AC XY: 8AN XY: 131946
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000226 AC: 33AN: 1461368Hom.: 0 Cov.: 175 AF XY: 0.0000179 AC XY: 13AN XY: 727016
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000184 AC: 28AN: 151920Hom.: 0 Cov.: 36 AF XY: 0.000242 AC XY: 18AN XY: 74234
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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.281G>A (p.S94N) alteration is located in exon 1 (coding exon 1) of the KRTAP10-4 gene. This alteration results from a G to A substitution at nucleotide position 281, causing the serine (S) at amino acid position 94 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Benign
.;N;.
REVEL
Benign
Sift
Benign
.;T;.
Sift4G
Benign
.;T;.
Vest4
0.26
MVP
0.44
MPC
0.42
ClinPred
T
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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