rs544705280

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031957.2(KRTAP1-5):​c.494G>T​(p.Arg165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R165C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KRTAP1-5
NM_031957.2 missense

Scores

2
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.325
Variant links:
Genes affected
KRTAP1-5 (HGNC:16777): (keratin associated protein 1-5) 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 high 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP1-5NM_031957.2 linkc.494G>T p.Arg165Leu missense_variant Exon 1 of 1 ENST00000361883.6 NP_114163.1 Q9BYS1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP1-5ENST00000361883.6 linkc.494G>T p.Arg165Leu missense_variant Exon 1 of 1 6 NM_031957.2 ENSP00000355302.5 Q9BYS1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1454556
Hom.:
0
Cov.:
31
AF XY:
0.00000415
AC XY:
3
AN XY:
722292
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:
0.00000181
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Uncertain
0.034
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.057
T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Benign
0.62
D
M_CAP
Benign
0.0079
T
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-0.34
T
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Benign
0.31
T
PROVEAN
Pathogenic
-6.1
D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.039
D
Polyphen
1.0
D
Vest4
0.34
MutPred
0.75
Loss of loop (P = 0.0986);
MVP
0.40
MPC
0.083
ClinPred
0.96
D
GERP RS
4.4
Varity_R
0.35
gMVP
0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39182914; API