11-71548917-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005553.4(KRTAP5-9):​c.260G>A​(p.Cys87Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

KRTAP5-9
NM_005553.4 missense

Scores

3
1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.778
Variant links:
Genes affected
KRTAP5-9 (HGNC:23604): (keratin associated protein 5-9) Enables identical protein binding activity. Predicted to be involved in epidermis development. 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11058164).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP5-9NM_005553.4 linkc.260G>A p.Cys87Tyr missense_variant Exon 1 of 1 ENST00000528743.4 NP_005544.4 P26371

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP5-9ENST00000528743.4 linkc.260G>A p.Cys87Tyr missense_variant Exon 1 of 1 6 NM_005553.4 ENSP00000431443.3 P26371

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000434
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251468
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.000370
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461030
Hom.:
0
Cov.:
31
AF XY:
0.00000826
AC XY:
6
AN XY:
726822
show subpopulations
Gnomad4 AFR exome
AF:
0.000419
Gnomad4 AMR exome
AF:
0.0000224
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:
0.000118
AC:
18
AN:
152342
Hom.:
0
Cov.:
33
AF XY:
0.0000805
AC XY:
6
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.000433
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.000455
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.260G>A (p.C87Y) alteration is located in exon 1 (coding exon 1) of the KRTAP5-9 gene. This alteration results from a G to A substitution at nucleotide position 260, causing the cysteine (C) at amino acid position 87 to be replaced by a tyrosine (Y). 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
0.16
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
11
DANN
Benign
0.60
DEOGEN2
Benign
0.072
T
Eigen
Benign
0.14
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.00083
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.9
H
PROVEAN
Pathogenic
-8.9
D
REVEL
Benign
0.041
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.96
D
Vest4
0.15
MVP
0.45
MPC
0.16
ClinPred
0.34
T
GERP RS
1.6
Varity_R
0.52

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: rs186626363; hg19: chr11-71259963; API