Variant 11-1598169-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004325.2(KRTAP5-2):c.82T>C(p.Cys28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,388,900 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000083 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000029 ( 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: 0.600

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:):

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=0.18802956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-2	NM_001004325.2 linkuse as main transcript	c.82T>C	p.Cys28Arg	missense_variant	1/1	ENST00000412090.2	NP_001004325.1	Q701N4
KRTAP5-AS1	NR_021489.2 linkuse as main transcript	n.1250A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-2	ENST00000412090.2 linkuse as main transcript	c.82T>C	p.Cys28Arg	missense_variant	1/1	6	NM_001004325.2	ENSP00000400041.1		Q701N4
KRTAP5-AS1	ENST00000424148.1 linkuse as main transcript	n.1250A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

120384

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000333

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000288

AC:

AN:

1388900

Hom.:

Cov.:

AF XY:

0.00000579

AC XY:

AN XY:

691186

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000282

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000831

AC:

AN:

120384

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

57028

show subpopulations

Gnomad4 AFR

AF:

0.0000333

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:

0.00

Gnomad4 OTH

AF:

0.00

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 submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.82T>C (p.C28R) alteration is located in exon 1 (coding exon 1) of the KRTAP5-2 gene. This alteration results from a T to C substitution at nucleotide position 82, causing the cysteine (C) at amino acid position 28 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

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.20

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.31

M_CAP

Benign

0.0032

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.2

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.086

Sift4G

Pathogenic

0.0

Polyphen

0.91

Vest4

0.36

MutPred

0.37

Gain of methylation at C28 (P = 0.0229);

MVP

0.18

MPC

0.16

ClinPred

0.42

GERP RS

1.9

Varity_R

0.67

gMVP

0.11

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