chr21-44592351-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_198688.3(KRTAP10-6):c.134C>T(p.Pro45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000052 ( 0 hom., cov: 1)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
KRTAP10-6
NM_198688.3 missense
NM_198688.3 missense
Scores
1
1
13
Clinical Significance
Conservation
PhyloP100: 1.03
Genes affected
KRTAP10-6 (HGNC:20523): (keratin associated protein 10-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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=0.124886215).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRTAP10-6 | NM_198688.3 | c.134C>T | p.Pro45Leu | missense_variant | 1/1 | ENST00000400368.1 | |
TSPEAR | NM_144991.3 | c.83-24346C>T | intron_variant | ENST00000323084.9 | |||
TSPEAR | NM_001272037.2 | c.-122-24346C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRTAP10-6 | ENST00000400368.1 | c.134C>T | p.Pro45Leu | missense_variant | 1/1 | NM_198688.3 | P1 | ||
TSPEAR | ENST00000323084.9 | c.83-24346C>T | intron_variant | 1 | NM_144991.3 | P1 | |||
TSPEAR | ENST00000642437.1 | c.*28-24346C>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000515 AC: 2AN: 38834Hom.: 0 Cov.: 1
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GnomAD3 exomes AF: 0.000105 AC: 23AN: 219268Hom.: 0 AF XY: 0.000109 AC XY: 13AN XY: 119438
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GnomAD4 exome AF: 0.00000285 AC: 2AN: 701950Hom.: 0 Cov.: 15 AF XY: 0.00000288 AC XY: 1AN XY: 347654
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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 | Aug 02, 2021 | The c.134C>T (p.P45L) alteration is located in exon 1 (coding exon 1) of the KRTAP10-6 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the proline (P) at amino acid position 45 to be replaced by a leucine (L). 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
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;N
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at