21-30396277-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181599.3(KRTAP13-1):ā€‹c.191C>Gā€‹(p.Thr64Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

KRTAP13-1
NM_181599.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.17
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.052814007).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRTAP13-1NM_181599.3 linkuse as main transcriptc.191C>G p.Thr64Ser missense_variant 1/1 ENST00000355459.4 NP_853630.2 Q8IUC0
LOC105372772XR_937653.3 linkuse as main transcriptn.196-2917G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRTAP13-1ENST00000355459.4 linkuse as main transcriptc.191C>G p.Thr64Ser missense_variant 1/16 NM_181599.3 ENSP00000347635.2 Q8IUC0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251280
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000544
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:
0.00000479
AC:
7
AN:
1461854
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
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
Cov.:
32
Bravo
AF:
0.0000264
ExAC
AF:
0.0000412
AC:
5

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 GeneticsJun 22, 2024The c.191C>G (p.T64S) alteration is located in exon 1 (coding exon 1) of the KRTAP13-1 gene. This alteration results from a C to G substitution at nucleotide position 191, causing the threonine (T) at amino acid position 64 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
0.092
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.040
DANN
Benign
0.84
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.010
N
LIST_S2
Benign
0.021
T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.053
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.024
Sift
Benign
0.17
T
Sift4G
Benign
0.42
T
Polyphen
0.72
P
Vest4
0.092
MutPred
0.36
Gain of glycosylation at T64 (P = 0.081);
MVP
0.23
MPC
0.20
ClinPred
0.085
T
GERP RS
-3.0
Varity_R
0.056
gMVP
0.018

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: rs774722882; hg19: chr21-31768595; API