17-41178145-C-T

Variant summary

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

The NM_033062.4(KRTAP4-2):​c.20G>A​(p.Gly7Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,600 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. G7V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KRTAP4-2
NM_033062.4 missense

Scores

2
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01
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]

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=0.20746046).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP4-2NM_033062.4 linkc.20G>A p.Gly7Asp 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.20G>A p.Gly7Asp missense_variant Exon 1 of 1 6 NM_033062.4 ENSP00000366955.2 Q9BYR5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460600
Hom.:
0
Cov.:
177
AF XY:
0.00000275
AC XY:
2
AN XY:
726452
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
21
DANN
Benign
0.81
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.073
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.6
H
PrimateAI
Benign
0.36
T
PROVEAN
Pathogenic
-6.6
D
REVEL
Benign
0.13
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.047
D
Polyphen
0.0010
B
Vest4
0.23
MutPred
0.50
Gain of relative solvent accessibility (P = 0.09);
MVP
0.40
MPC
0.12
ClinPred
0.27
T
GERP RS
2.7
Varity_R
0.31
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39334397; API