chr21-44573880-G-C

Variant summary

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

The NM_198687.2(KRTAP10-4):ā€‹c.122G>Cā€‹(p.Cys41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000067 ( 0 hom., cov: 47)
Exomes š‘“: 0.0000041 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KRTAP10-4
NM_198687.2 missense

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.939
Variant links:
Genes affected
KRTAP10-4 (HGNC:20521): (keratin associated protein 10-4) This is an intronless gene located in a cluster of related genes on the q arm of chromosome 21. The proteins encoded by these genes form disulfide bonds with cysteine residues in hair keratins, thereby contributing to the structure and stability of hair fibers. [provided by RefSeq, Apr 2014]
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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRTAP10-4NM_198687.2 linkc.122G>C p.Cys41Ser missense_variant 1/1 ENST00000400374.4 NP_941960.2 P60372
TSPEARNM_144991.3 linkc.83-5875C>G intron_variant ENST00000323084.9 NP_659428.2 Q8WU66-1
TSPEARNM_001272037.2 linkc.-122-5875C>G intron_variant NP_001258966.1 Q8WU66

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRTAP10-4ENST00000400374.4 linkc.122G>C p.Cys41Ser missense_variant 1/16 NM_198687.2 ENSP00000383225.3 P60372
TSPEARENST00000323084.9 linkc.83-5875C>G intron_variant 1 NM_144991.3 ENSP00000321987.4 Q8WU66-1
TSPEARENST00000642437.1 linkn.*28-5875C>G intron_variant ENSP00000496535.1 A0A2R8YFK6

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
149726
Hom.:
0
Cov.:
47
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000407
AC:
1
AN:
245646
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133500
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:
0.00000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000411
AC:
6
AN:
1459218
Hom.:
0
Cov.:
234
AF XY:
0.00000551
AC XY:
4
AN XY:
725998
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000668
AC:
1
AN:
149726
Hom.:
0
Cov.:
47
AF XY:
0.00
AC XY:
0
AN XY:
73212
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000852
AC:
1

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 submitterclinical testingAmbry GeneticsOct 08, 2024The c.122G>C (p.C41S) alteration is located in exon 1 (coding exon 1) of the KRTAP10-4 gene. This alteration results from a G to C substitution at nucleotide position 122, causing the cysteine (C) at amino acid position 41 to be replaced by a serine (S). 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
0.17
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
21
DANN
Benign
0.96
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.72
T;.;T
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.24
T
PROVEAN
Pathogenic
-8.1
.;D;.
REVEL
Benign
0.15
Sift
Uncertain
0.0020
.;D;.
Sift4G
Benign
0.14
.;T;.
Vest4
0.32
MutPred
0.52
.;Gain of glycosylation at C41 (P = 0.0017);.;
MVP
0.36
MPC
1.5
ClinPred
0.95
D
GERP RS
4.5
gMVP
0.13

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: rs782350749; hg19: chr21-45993757; API