rs142700218

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198695.2(KRTAP10-8):​c.218C>A​(p.Ala73Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A73V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

KRTAP10-8
NM_198695.2 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.239
Variant links:
Genes affected
KRTAP10-8 (HGNC:20525): (keratin associated protein 10-8) Enables identical protein binding activity. 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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07821676).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP10-8NM_198695.2 linkc.218C>A p.Ala73Asp missense_variant Exon 1 of 1 ENST00000334662.2 NP_941968.2 P60410
TSPEARNM_144991.3 linkc.83-44313G>T intron_variant Intron 1 of 11 ENST00000323084.9 NP_659428.2 Q8WU66-1
TSPEARNM_001272037.2 linkc.-122-44313G>T intron_variant Intron 2 of 12 NP_001258966.1 Q8WU66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP10-8ENST00000334662.2 linkc.218C>A p.Ala73Asp missense_variant Exon 1 of 1 6 NM_198695.2 ENSP00000335565.2 P60410
TSPEARENST00000323084.9 linkc.83-44313G>T intron_variant Intron 1 of 11 1 NM_144991.3 ENSP00000321987.4 Q8WU66-1
TSPEARENST00000642437.1 linkn.*28-44313G>T intron_variant Intron 2 of 12 ENSP00000496535.1 A0A2R8YFK6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
16
DANN
Benign
0.75
DEOGEN2
Benign
0.0056
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.074
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.34
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.040
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0050
D
Polyphen
0.41
B
Vest4
0.19
MutPred
0.37
Gain of loop (P = 0.0851);
MVP
0.26
MPC
0.10
ClinPred
0.14
T
GERP RS
-0.82
Varity_R
0.42
gMVP
0.056

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142700218; hg19: chr21-46032235; API