21-30371996-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.218C>G​(p.Ser73Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,738 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

KRTAP13-2
NM_181621.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.335
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=0.29549497).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP13-2NM_181621.4 linkc.218C>G p.Ser73Cys 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.218C>G p.Ser73Cys missense_variant Exon 1 of 1 6 NM_181621.4 ENSP00000382777.2 Q52LG2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251056
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135656
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461738
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727192
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
Cov.:
32
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.218C>G (p.S73C) 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 218, causing the serine (S) at amino acid position 73 to be replaced by a cysteine (C). 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
0.15
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.056
T
Eigen
Benign
-0.0022
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.071
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.087
T
Polyphen
1.0
D
Vest4
0.31
MutPred
0.43
Loss of glycosylation at S73 (P = 0.0328);
MVP
0.24
MPC
0.26
ClinPred
0.89
D
GERP RS
0.15
Varity_R
0.58
gMVP
0.030

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs754151542; hg19: chr21-31744314; API