ENST00000394008.1:c.413C>T

Variant summary

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

The ENST00000394008.1(KRTAP9-9):​c.413C>T​(p.Pro138Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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. P138H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KRTAP9-9
ENST00000394008.1 missense

Scores

1
3
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90
Variant links:
Genes affected
KRTAP9-9 (HGNC:16773): (keratin associated protein 9-9) 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. Alternative haplotypes of this gene are represented in the GRCh38 reference genome assembly. [provided by RefSeq, Dec 2015]

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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=0.16892445).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP9-9NM_030975.2 linkc.413C>T p.Pro138Leu missense_variant Exon 1 of 1 NP_112237.2 Q9BYP9-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP9-9ENST00000394008.1 linkc.413C>T p.Pro138Leu missense_variant Exon 1 of 1 6 ENSP00000377576.1 Q9BYP9-3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461550
Hom.:
0
Cov.:
36
AF XY:
0.00000138
AC XY:
1
AN XY:
727040
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
20
DANN
Uncertain
0.99
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.12
N
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.24
T
PROVEAN
Pathogenic
-7.3
D
REVEL
Benign
0.077
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.0080
D
Vest4
0.27
MVP
0.19
MPC
0.24
ClinPred
0.95
D
GERP RS
1.9
gMVP
0.069

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: chr17-39412050; API