21-30396367-C-G

Variant summary

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

The NM_181599.3(KRTAP13-1):​c.281C>G​(p.Thr94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,894 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. T94A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

KRTAP13-1
NM_181599.3 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.219
Variant links:
Genes affected
KRTAP13-1 (HGNC:18924): (keratin associated protein 13-1) Hair keratins and hair keratin-associated proteins (KAPs), such as KRTAP13-1, are the main structural proteins of hair fibers (Rogers et al., 2002 [PubMed 12359730]).[supplied by OMIM, Mar 2008]

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=0.34090352).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP13-1NM_181599.3 linkc.281C>G p.Thr94Arg missense_variant Exon 1 of 1 ENST00000355459.4 NP_853630.2 Q8IUC0
LOC105372772XR_937653.3 linkn.196-3007G>C intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP13-1ENST00000355459.4 linkc.281C>G p.Thr94Arg missense_variant Exon 1 of 1 6 NM_181599.3 ENSP00000347635.2 Q8IUC0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251416
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000205
AC:
3
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
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:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
11
DANN
Uncertain
0.98
DEOGEN2
Benign
0.060
T
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.065
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.10
Sift
Uncertain
0.018
D
Sift4G
Uncertain
0.039
D
Polyphen
0.99
D
Vest4
0.43
MutPred
0.31
Gain of solvent accessibility (P = 0.0503);
MVP
0.33
MPC
0.27
ClinPred
0.81
D
GERP RS
0.56
Varity_R
0.25
gMVP
0.083

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: rs368397128; hg19: chr21-31768685; API