rs781983764

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198695.2(KRTAP10-8):​c.185C>A​(p.Thr62Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,410 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T62I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

KRTAP10-8
NM_198695.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06429702).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP10-8NM_198695.2 linkc.185C>A p.Thr62Asn missense_variant Exon 1 of 1 ENST00000334662.2 NP_941968.2 P60410
TSPEARNM_144991.3 linkc.83-44280G>T intron_variant Intron 1 of 11 ENST00000323084.9 NP_659428.2 Q8WU66-1
TSPEARNM_001272037.2 linkc.-122-44280G>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.185C>A p.Thr62Asn missense_variant Exon 1 of 1 6 NM_198695.2 ENSP00000335565.2 P60410
TSPEARENST00000323084.9 linkc.83-44280G>T intron_variant Intron 1 of 11 1 NM_144991.3 ENSP00000321987.4 Q8WU66-1
TSPEARENST00000642437.1 linkn.*28-44280G>T intron_variant Intron 2 of 12 ENSP00000496535.1 A0A2R8YFK6

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250632
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135516
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461258
Hom.:
0
Cov.:
35
AF XY:
0.00000825
AC XY:
6
AN XY:
726962
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
8.3
DANN
Benign
0.84
DEOGEN2
Benign
0.015
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.00073
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.064
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.90
L
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.040
Sift
Benign
0.087
T
Sift4G
Benign
0.44
T
Polyphen
0.58
P
Vest4
0.18
MutPred
0.24
Loss of phosphorylation at T62 (P = 0.0896);
MVP
0.27
MPC
0.082
ClinPred
0.071
T
GERP RS
-2.5
Varity_R
0.12
gMVP
0.022

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: rs781983764; hg19: chr21-46032202; API