chr11-1607869-G-A

Variant summary

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

The NM_001012708.2(KRTAP5-3):​c.517C>T​(p.Pro173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,600,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

KRTAP5-3
NM_001012708.2 missense

Scores

1
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0330
Variant links:
Genes affected
KRTAP5-3 (HGNC:23598): (keratin associated protein 5-3) 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 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=0.0326021).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRTAP5-3NM_001012708.2 linkuse as main transcriptc.517C>T p.Pro173Ser missense_variant 1/1 ENST00000399685.1 NP_001012726.1 Q6L8H2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRTAP5-3ENST00000399685.1 linkuse as main transcriptc.517C>T p.Pro173Ser missense_variant 1/16 NM_001012708.2 ENSP00000382592.1 Q6L8H2

Frequencies

GnomAD3 genomes
AF:
0.000166
AC:
25
AN:
150496
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000245
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000664
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00127
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000251
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
251096
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135744
show subpopulations
Gnomad AFR exome
AF:
0.0000620
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000134
AC:
195
AN:
1450224
Hom.:
0
Cov.:
137
AF XY:
0.000164
AC XY:
118
AN XY:
721078
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000775
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.0000896
Gnomad4 OTH exome
AF:
0.000318
GnomAD4 genome
AF:
0.000166
AC:
25
AN:
150496
Hom.:
0
Cov.:
29
AF XY:
0.000150
AC XY:
11
AN XY:
73320
show subpopulations
Gnomad4 AFR
AF:
0.0000245
Gnomad4 AMR
AF:
0.0000664
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00127
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000251
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000199
Hom.:
0
Bravo
AF:
0.000162
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000313
AC:
38
EpiCase
AF:
0.000493
EpiControl
AF:
0.000179

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 GeneticsApr 24, 2023The c.517C>T (p.P173S) alteration is located in exon 1 (coding exon 1) of the KRTAP5-3 gene. This alteration results from a C to T substitution at nucleotide position 517, causing the proline (P) at amino acid position 173 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
0.28
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
16
DANN
Benign
0.83
DEOGEN2
Benign
0.099
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0044
N
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.033
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.5
M
PROVEAN
Pathogenic
-6.1
D
REVEL
Benign
0.040
Sift
Uncertain
0.014
D
Sift4G
Benign
0.13
T
Polyphen
0.0010
B
Vest4
0.14
MVP
0.081
MPC
0.021
ClinPred
0.14
T
GERP RS
-0.16
Varity_R
0.16
gMVP
0.037

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.20
Position offset: 6

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: rs201674720; hg19: chr11-1629099; API