17-41184442-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001386841.1(KRTAP4-1):​c.413G>A​(p.Arg138His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,603,788 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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. R138C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0059 ( 13 hom., cov: 34)
Exomes 𝑓: 0.00057 ( 7 hom. )

Consequence

KRTAP4-1
NM_001386841.1 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.369
Variant links:
Genes affected
KRTAP4-1 (HGNC:18907): (keratin associated protein 4-1) 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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0049245656).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0059 (898/152306) while in subpopulation AFR AF= 0.0206 (858/41554). AF 95% confidence interval is 0.0195. There are 13 homozygotes in gnomad4. There are 426 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP4-1NM_001386841.1 linkc.413G>A p.Arg138His missense_variant Exon 1 of 1 ENST00000398472.2 NP_001373770.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP4-1ENST00000398472.2 linkc.413G>A p.Arg138His missense_variant Exon 1 of 1 6 NM_001386841.1 ENSP00000381489.1 Q9BYQ7

Frequencies

GnomAD3 genomes
AF:
0.00586
AC:
892
AN:
152188
Hom.:
13
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0206
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00209
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:
0.0000294
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00141
AC:
346
AN:
244672
Hom.:
2
AF XY:
0.00113
AC XY:
149
AN XY:
132342
show subpopulations
Gnomad AFR exome
AF:
0.0202
Gnomad AMR exome
AF:
0.000669
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000548
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000722
Gnomad OTH exome
AF:
0.000336
GnomAD4 exome
AF:
0.000573
AC:
832
AN:
1451482
Hom.:
7
Cov.:
77
AF XY:
0.000473
AC XY:
341
AN XY:
720248
show subpopulations
Gnomad4 AFR exome
AF:
0.0199
Gnomad4 AMR exome
AF:
0.000810
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000470
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000380
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
AF:
0.00590
AC:
898
AN:
152306
Hom.:
13
Cov.:
34
AF XY:
0.00572
AC XY:
426
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0206
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.000846
Hom.:
1
Bravo
AF:
0.00667
ESP6500AA
AF:
0.0185
AC:
80
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00181
AC:
219
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.72
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
8.2
DANN
Benign
0.90
DEOGEN2
Benign
0.079
T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.13
T;T
MetaRNN
Benign
0.0049
T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Benign
0.19
T
PROVEAN
Uncertain
-3.1
.;D
REVEL
Benign
0.028
Sift
Uncertain
0.024
.;D
Sift4G
Benign
0.066
T;T
Polyphen
0.019
.;B
Vest4
0.18
MVP
0.030
MPC
0.20
ClinPred
0.016
T
GERP RS
1.9
Varity_R
0.059
gMVP
0.055

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: rs112363564; hg19: chr17-39340694; COSMIC: COSV66648133; COSMIC: COSV66648133; API