Genetic Variant KRTAP5-1:p.Gly88Ala (chr11-1584987-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001005922.1(KRTAP5-1):c.263G>C(p.Gly88Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000504 in 1,389,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 𝑓 0.0000090 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

KRTAP5-1
NM_001005922.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.136

Variant links:

Genes affected

KRTAP5-1 (HGNC:23596): (keratin associated protein 5-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-1 links:

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

KRTAP5-AS1 links:

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=0.12717059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-1	NM_001005922.1 link	c.263G>C	p.Gly88Ala	missense_variant	Exon 1 of 1	ENST00000382171.2	NP_001005922.1	Q6L8H4
KRTAP5-AS1	NR_021489.2 link	n.328+11919C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-1	ENST00000382171.2 link	c.263G>C	p.Gly88Ala	missense_variant	Exon 1 of 1	6	NM_001005922.1	ENSP00000371606.2		Q6L8H4

Frequencies

GnomAD3 genomes

AF:

0.00000902

AC:

AN:

110900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000184

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245870

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000906

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000469

AC:

AN:

1278778

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

634878

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:

0.00000603

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000902

AC:

AN:

110900

Hom.:

Cov.:

AF XY:

0.0000189

AC XY:

AN XY:

53042

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000184

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.11

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.23

M_CAP

Benign

0.0058

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.042

Sift

Pathogenic

0.0

Sift4G

Benign

0.22

Polyphen

0.60

Vest4

0.27

MutPred

0.21

Gain of glycosylation at K86 (P = 0.1264);

MVP

0.18

MPC

0.044

ClinPred

0.29

GERP RS

2.8

Varity_R

0.14

gMVP

0.041

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over