Genetic Variant KRTAP5-1:p.Gly200Ser (chr11-1584652-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005922.1(KRTAP5-1):c.598G>A(p.Gly200Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,445,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.000046 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP5-1
NM_001005922.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.04

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03426501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-1	NM_001005922.1 link	c.598G>A	p.Gly200Ser	missense_variant	Exon 1 of 1	ENST00000382171.2	NP_001005922.1	Q6L8H4
KRTAP5-AS1	NR_021489.2 link	n.328+11584C>T		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.598G>A	p.Gly200Ser	missense_variant	Exon 1 of 1	6	NM_001005922.1	ENSP00000371606.2		Q6L8H4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

107632

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000689

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000259

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000203

Gnomad OTH

AF:

0.000699

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1445766

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

719126

show subpopulations

Gnomad4 AFR exome

AF:

0.0000607

Gnomad4 AMR exome

AF:

0.0000228

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:

0.0000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000464

AC:

AN:

107748

Hom.:

Cov.:

AF XY:

0.0000574

AC XY:

AN XY:

52280

show subpopulations

Gnomad4 AFR

AF:

0.0000686

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000259

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000203

Gnomad4 OTH

AF:

0.000692

Alfa

AF:

0.0000450

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.598G>A (p.G200S) alteration is located in exon 1 (coding exon 1) of the KRTAP5-1 gene. This alteration results from a G to A substitution at nucleotide position 598, causing the glycine (G) at amino acid position 200 to be replaced by a serine (S). 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

0.064

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.19

DANN

Benign

0.75

DEOGEN2

Benign

0.0077

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0010

M_CAP

Benign

0.0013

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

PROVEAN

Benign

0.51

REVEL

Benign

0.014

Sift

Pathogenic

0.0

Sift4G

Benign

1.0

Polyphen

0.086

Vest4

0.15

MVP

0.081

MPC

0.041

ClinPred

0.070

GERP RS

-5.4

Varity_R

0.059

gMVP

0.014

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over