21-44539538-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198691.3(KRTAP10-1):c.613G>A(p.Gly205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,612,712 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00066 ( 1 hom. )
Consequence
KRTAP10-1
NM_198691.3 missense
NM_198691.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: -0.421
Genes affected
KRTAP10-1 (HGNC:22966): (keratin associated protein 10-1) This gene encodes a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This gene encodes a member of the high sulfur KAP family. It is localized to a cluster of intronless KAPs at 21q22.3 which are located within the introns of the C21orf29 gene. [provided by RefSeq, Jul 2008]
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| KRTAP10-1 | NM_198691.3 | c.613G>A | p.Gly205Arg | missense_variant | 1/1 | ENST00000400375.1 | NP_941964.2 | |
| TSPEAR | NM_144991.3 | c.304-5615G>A | intron_variant | ENST00000323084.9 | NP_659428.2 | |||
| TSPEAR | NM_001272037.2 | c.100-5615G>A | intron_variant | NP_001258966.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| KRTAP10-1 | ENST00000400375.1 | c.613G>A | p.Gly205Arg | missense_variant | 1/1 | NM_198691.3 | ENSP00000383226 | P1 | ||
| TSPEAR | ENST00000323084.9 | c.304-5615G>A | intron_variant | 1 | NM_144991.3 | ENSP00000321987 | P1 | |||
| TSPEAR | ENST00000397916.1 | n.259-5615G>A | intron_variant, non_coding_transcript_variant | 1 | ||||||
| TSPEAR | ENST00000642437.1 | c.*249-5615G>A | intron_variant, NMD_transcript_variant | ENSP00000496535 |
Frequencies
GnomAD3 genomes 0.000377 AC: 57AN: 151140Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000422 AC: 106AN: 251350Hom.: 0 AF XY: 0.000397 AC XY: 54AN XY: 135852
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GnomAD4 exome AF: 0.000657 AC: 960AN: 1461466Hom.: 1 Cov.: 174 AF XY: 0.000629 AC XY: 457AN XY: 727034
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GnomAD4 genome 0.000377 AC: 57AN: 151246Hom.: 0 Cov.: 33 AF XY: 0.000365 AC XY: 27AN XY: 73930
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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 19, 2021 | The c.613G>A (p.G205R) alteration is located in exon 1 (coding exon 1) of the KRTAP10-1 gene. This alteration results from a G to A substitution at nucleotide position 613, causing the glycine (G) at amino acid position 205 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
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of glycosylation at S204 (P = 0.0423);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at