21-44646547-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198692.3(KRTAP10-11):​c.89C>T​(p.Pro30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. P30R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KRTAP10-11
NM_198692.3 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.936
Variant links:
Genes affected
KRTAP10-11 (HGNC:20528): (keratin associated protein 10-11) 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.

BP4
Computational evidence support a benign effect (MetaRNN=0.14703652).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP10-11NM_198692.3 linkc.89C>T p.Pro30Leu missense_variant Exon 1 of 1 ENST00000334670.9 NP_941965.2 P60411P60412
TSPEARNM_144991.3 linkc.82+64886G>A intron_variant Intron 1 of 11 ENST00000323084.9 NP_659428.2 Q8WU66-1
TSPEARNM_001272037.2 linkc.-123+43998G>A intron_variant Intron 2 of 12 NP_001258966.1 Q8WU66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP10-11ENST00000334670.9 linkc.89C>T p.Pro30Leu missense_variant Exon 1 of 1 6 NM_198692.3 ENSP00000334197.8 P60412
TSPEARENST00000323084.9 linkc.82+64886G>A intron_variant Intron 1 of 11 1 NM_144991.3 ENSP00000321987.4 Q8WU66-1
TSPEARENST00000642437.1 linkn.*27+43998G>A intron_variant Intron 2 of 12 ENSP00000496535.1 A0A2R8YFK6

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000321
AC:
8
AN:
249222
Hom.:
0
AF XY:
0.0000517
AC XY:
7
AN XY:
135276
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:
0.000262
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000205
AC:
30
AN:
1460300
Hom.:
0
Cov.:
154
AF XY:
0.0000317
AC XY:
23
AN XY:
726456
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.000302
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.057
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.17
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.21
T
PROVEAN
Pathogenic
-7.9
D
REVEL
Benign
0.10
Sift
Benign
0.069
T
Sift4G
Uncertain
0.036
D
Polyphen
0.94
P
Vest4
0.24
MutPred
0.34
Loss of catalytic residue at P29 (P = 0.0179);
MVP
0.30
MPC
0.013
ClinPred
0.30
T
GERP RS
1.4
Varity_R
0.15
gMVP
0.057

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs377177017; hg19: chr21-46066464; COSMIC: COSV58178776; API