Genetic Variant KRTAP5-2:p.Lys95Arg (chr11-1597967-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004325.2(KRTAP5-2):c.284A>G(p.Lys95Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000044 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP5-2
NM_001004325.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.291

Variant links:

Genes affected

KRTAP5-2 (HGNC:23597): (keratin associated protein 5-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-2 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.071309745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-2	NM_001004325.2 link	c.284A>G	p.Lys95Arg	missense_variant	Exon 1 of 1	ENST00000412090.2	NP_001004325.1	Q701N4
KRTAP5-AS1	NR_021489.2 link	n.1048T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRTAP5-2	ENST00000412090.2 link	c.284A>G	p.Lys95Arg	missense_variant	Exon 1 of 1	6	NM_001004325.2	ENSP00000400041.1	Q701N4
KRTAP5-AS1	ENST00000424148.1 link	n.1048T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2
KRTAP5-AS1	ENST00000659213.1 link	n.*59T>C		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

11416

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00423

Gnomad ASJ

AF:

0.00546

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000379

Gnomad OTH

AF:

0.00602

GnomAD3 exomes

AF:

0.0000291

AC:

AN:

240886

Hom.:

AF XY:

0.0000382

AC XY:

AN XY:

130748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000620

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000914

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000437

AC:

AN:

343324

Hom.:

Cov.:

AF XY:

0.0000532

AC XY:

AN XY:

169144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00171

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.000317

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00157

AC:

AN:

11464

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

AN XY:

5936

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00420

Gnomad4 ASJ

AF:

0.00546

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00165

Gnomad4 NFE

AF:

0.000379

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0439

Hom.:

ExAC

AF:

0.0000197

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.284A>G (p.K95R) alteration is located in exon 1 (coding exon 1) of the KRTAP5-2 gene. This alteration results from a A to G substitution at nucleotide position 284, causing the lysine (K) at amino acid position 95 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.084

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.016

M_CAP

Benign

0.011

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.3

PROVEAN

Benign

-0.29

REVEL

Benign

0.096

Sift4G

Benign

0.36

Polyphen

0.030

Vest4

0.35

MutPred

0.28

Loss of methylation at K95 (P = 0.0036);

MVP

0.25

MPC

0.072

ClinPred

0.051

GERP RS

3.6

Varity_R

0.16

gMVP

0.035

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over