21-44600833-C-T

Variant summary

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

The NM_198689.3(KRTAP10-7):​c.212C>T​(p.Thr71Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KRTAP10-7
NM_198689.3 missense

Scores

1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.178
Variant links:
Genes affected
KRTAP10-7 (HGNC:22970): (keratin associated protein 10-7) 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 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=0.103397906).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP10-7NM_198689.3 linkc.212C>T p.Thr71Ile missense_variant Exon 1 of 1 ENST00000609664.2 NP_941962.1 P60409
TSPEARNM_144991.3 linkc.83-32828G>A intron_variant Intron 1 of 11 ENST00000323084.9 NP_659428.2 Q8WU66-1
TSPEARNM_001272037.2 linkc.-122-32828G>A intron_variant Intron 2 of 12 NP_001258966.1 Q8WU66

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP10-7ENST00000609664.2 linkc.212C>T p.Thr71Ile missense_variant Exon 1 of 1 6 NM_198689.3 ENSP00000476821.1 P60409
TSPEARENST00000323084.9 linkc.83-32828G>A intron_variant Intron 1 of 11 1 NM_144991.3 ENSP00000321987.4 Q8WU66-1
TSPEARENST00000642437.1 linkn.*28-32828G>A intron_variant Intron 2 of 12 ENSP00000496535.1 A0A2R8YFK6

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
136820
Hom.:
0
Cov.:
31
FAILED QC
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1451090
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
722072
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:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
136820
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
66576
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:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000353
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.212C>T (p.T71I) alteration is located in exon 1 (coding exon 1) of the KRTAP10-7 gene. This alteration results from a C to T substitution at nucleotide position 212, causing the threonine (T) at amino acid position 71 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
15
DANN
Uncertain
0.99
Eigen
Benign
-0.99
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0045
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.95
T
PrimateAI
Benign
0.21
T
Sift4G
Benign
0.12
T
Vest4
0.10
MVP
0.37
ClinPred
0.069
T
GERP RS
-0.63
Varity_R
0.042
gMVP
0.030

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs782792430; hg19: chr21-46020748; API