17-41315532-C-T

Variant summary

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

The NM_031964.2(KRTAP17-1):​c.119G>A​(p.Gly40Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KRTAP17-1
NM_031964.2 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06
Variant links:
Genes affected
KRTAP17-1 (HGNC:18917): (keratin associated protein 17-1) 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]

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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/exons MANE Protein UniProt
KRTAP17-1NM_031964.2 linkc.119G>A p.Gly40Asp missense_variant 1/1 ENST00000334202.5 NP_114170.1 Q9BYP8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRTAP17-1ENST00000334202.5 linkc.119G>A p.Gly40Asp missense_variant 1/16 NM_031964.2 ENSP00000333993.3 Q9BYP8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456170
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
724134
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:
0.0000190
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 08, 2024The c.119G>A (p.G40D) alteration is located in exon 1 (coding exon 1) of the KRTAP17-1 gene. This alteration results from a G to A substitution at nucleotide position 119, causing the glycine (G) at amino acid position 40 to be replaced by an aspartic acid (D). 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
0.32
BayesDel_addAF
Benign
-0.0080
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
18
DANN
Benign
0.87
DEOGEN2
Benign
0.0072
T
Eigen
Benign
-0.060
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.24
N
M_CAP
Benign
0.025
T
MetaRNN
Uncertain
0.47
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.25
N
REVEL
Benign
0.15
Sift4G
Uncertain
0.032
D
Polyphen
1.0
D
Vest4
0.52
MutPred
0.18
Gain of solvent accessibility (P = 0.1014);
MVP
0.42
MPC
0.30
ClinPred
0.23
T
GERP RS
3.9
Varity_R
0.16
gMVP
0.096

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr17-39471784; API