NM_033062.4:c.230G>A

Variant summary

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

The NM_033062.4(KRTAP4-2):​c.230G>A​(p.Arg77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,612,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R77L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

KRTAP4-2
NM_033062.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95
Variant links:
Genes affected
KRTAP4-2 (HGNC:18900): (keratin associated protein 4-2) 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]

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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=0.18515769).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP4-2NM_033062.4 linkc.230G>A p.Arg77His missense_variant Exon 1 of 1 ENST00000377726.3 NP_149051.2 Q9BYR5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP4-2ENST00000377726.3 linkc.230G>A p.Arg77His missense_variant Exon 1 of 1 6 NM_033062.4 ENSP00000366955.2 Q9BYR5

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
151912
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
249944
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135548
show subpopulations
Gnomad AFR exome
AF:
0.0000642
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1460714
Hom.:
0
Cov.:
180
AF XY:
0.0000179
AC XY:
13
AN XY:
726720
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
151912
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74182
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.12
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Benign
0.17
T
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.033
Sift
Uncertain
0.021
D
Sift4G
Benign
0.093
T
Polyphen
1.0
D
Vest4
0.072
MutPred
0.50
Gain of glycosylation at S79 (P = 0.072);
MVP
0.45
MPC
0.21
ClinPred
0.32
T
GERP RS
0.49
Varity_R
0.084
gMVP
0.054

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: rs771456494; hg19: chr17-39334187; COSMIC: COSV66658150; API