17-41238213-C-G

Variant summary

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

The NM_031963.3(KRTAP9-8):​c.162C>G​(p.Asn54Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,607,930 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.00023 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

KRTAP9-8
NM_031963.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.546
Variant links:
Genes affected
KRTAP9-8 (HGNC:17231): (keratin associated protein 9-8) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

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=0.099696696).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP9-8NM_031963.3 linkc.162C>G p.Asn54Lys missense_variant Exon 1 of 1 ENST00000254072.7 NP_114169.2 Q9BYQ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP9-8ENST00000254072.7 linkc.162C>G p.Asn54Lys missense_variant Exon 1 of 1 6 NM_031963.3 ENSP00000254072.6 Q9BYQ0

Frequencies

GnomAD3 genomes
AF:
0.000229
AC:
34
AN:
148304
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
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:
0.000412
Gnomad OTH
AF:
0.000483
GnomAD3 exomes
AF:
0.000200
AC:
50
AN:
250590
Hom.:
0
AF XY:
0.000184
AC XY:
25
AN XY:
135534
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
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:
0.000360
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000460
AC:
671
AN:
1459626
Hom.:
0
Cov.:
31
AF XY:
0.000443
AC XY:
322
AN XY:
726216
show subpopulations
Gnomad4 AFR exome
AF:
0.000222
Gnomad4 AMR exome
AF:
0.000179
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:
0.000572
Gnomad4 OTH exome
AF:
0.000332
GnomAD4 genome
AF:
0.000229
AC:
34
AN:
148304
Hom.:
1
Cov.:
31
AF XY:
0.000166
AC XY:
12
AN XY:
72474
show subpopulations
Gnomad4 AFR
AF:
0.000106
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000412
Gnomad4 OTH
AF:
0.000483
Alfa
AF:
0.000395
Hom.:
0
Bravo
AF:
0.000238
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000116
AC:
14
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 19, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.162C>G (p.N54K) alteration is located in exon 1 (coding exon 1) of the KRTAP9-8 gene. This alteration results from a C to G substitution at nucleotide position 162, causing the asparagine (N) at amino acid position 54 to be replaced by a lysine (K). 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
0.29
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
13
DANN
Benign
0.87
DEOGEN2
Benign
0.031
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.031
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.059
Sift
Uncertain
0.023
D
Sift4G
Uncertain
0.046
D
Polyphen
0.81
P
Vest4
0.32
MutPred
0.42
Gain of methylation at N54 (P = 0.0022);
MVP
0.040
MPC
0.25
ClinPred
0.96
D
GERP RS
0.12
Varity_R
0.13
gMVP
0.046

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: rs200718914; hg19: chr17-39394465; API