21-30372177-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181621.4(KRTAP13-2):​c.37C>G​(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

KRTAP13-2
NM_181621.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.01
Variant links:
Genes affected
KRTAP13-2 (HGNC:18923): (keratin associated protein 13-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30268517).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP13-2NM_181621.4 linkc.37C>G p.Arg13Gly missense_variant Exon 1 of 1 ENST00000399889.4 NP_853652.1 Q52LG2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP13-2ENST00000399889.4 linkc.37C>G p.Arg13Gly missense_variant Exon 1 of 1 6 NM_181621.4 ENSP00000382777.2 Q52LG2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250610
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135360
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461578
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727064
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000895
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.37C>G (p.R13G) alteration is located in exon 1 (coding exon 1) of the KRTAP13-2 gene. This alteration results from a C to G substitution at nucleotide position 37, causing the arginine (R) at amino acid position 13 to be replaced by a glycine (G). 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
-0.38
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
14
DANN
Benign
0.97
DEOGEN2
Benign
0.0054
T
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.20
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Benign
0.062
Sift
Benign
0.071
T
Sift4G
Benign
0.46
T
Polyphen
0.94
P
Vest4
0.39
MutPred
0.68
Gain of glycosylation at S12 (P = 0.0635);
MVP
0.13
MPC
0.088
ClinPred
0.88
D
GERP RS
0.036
Varity_R
0.24
gMVP
0.030

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs149187693; hg19: chr21-31744495; API