21-44574048-T-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_198687.2(KRTAP10-4):āc.290T>Cā(p.Leu97Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.00063 ( 0 hom., cov: 36)
Exomes š: 0.000054 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KRTAP10-4
NM_198687.2 missense
NM_198687.2 missense
Scores
9
Clinical Significance
Conservation
PhyloP100: -0.380
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 -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_addAF=-0.329124).
BP6
Variant 21-44574048-T-C is Benign according to our data. Variant chr21-44574048-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2352184.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRTAP10-4 | NM_198687.2 | c.290T>C | p.Leu97Pro | missense_variant | 1/1 | ENST00000400374.4 | |
TSPEAR | NM_144991.3 | c.83-6043A>G | intron_variant | ENST00000323084.9 | |||
TSPEAR | NM_001272037.2 | c.-122-6043A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRTAP10-4 | ENST00000400374.4 | c.290T>C | p.Leu97Pro | missense_variant | 1/1 | NM_198687.2 | P1 | ||
TSPEAR | ENST00000323084.9 | c.83-6043A>G | intron_variant | 1 | NM_144991.3 | P1 | |||
TSPEAR | ENST00000642437.1 | c.*28-6043A>G | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 89AN: 141402Hom.: 0 Cov.: 36 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000543 AC: 79AN: 1456024Hom.: 0 Cov.: 176 AF XY: 0.0000566 AC XY: 41AN XY: 724424
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000629 AC: 89AN: 141518Hom.: 0 Cov.: 36 AF XY: 0.000563 AC XY: 39AN XY: 69226
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 01, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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
MutationTaster
Benign
N;N
ClinPred
T
GERP RS
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