Variant 17-41059854-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001165252.2(KRTAP2-3):c.197C>T(p.Pro66Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000066 in 151,534 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP2-3
NM_001165252.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

Variant links:

Genes affected

KRTAP2-3 (HGNC:18906): (keratin associated protein 2-3) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP2-3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-3	NM_001165252.2 linkuse as main transcript	c.197C>T	p.Pro66Leu	missense_variant	1/1	ENST00000391418.3	NP_001158724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP2-3	ENST00000391418.3 linkuse as main transcript	c.197C>T	p.Pro66Leu	missense_variant	1/1		NM_001165252.2	ENSP00000375237	P1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

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

Data not reliable, filtered out with message: AS_VQSR

AF:

7.28e-7

AC:

AN:

1372748

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675250

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:

9.34e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151534

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73984

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000660

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

Bravo

AF:

0.00000378

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

Oct 29, 2021

The c.197C>T (p.P66L) alteration is located in exon 1 (coding exon 1) of the KRTAP2-3 gene. This alteration results from a C to T substitution at nucleotide position 197, causing the proline (P) at amino acid position 66 to be replaced by a leucine (L). 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

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.047

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.73

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.7

REVEL

Benign

0.26

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.030

Vest4

0.57

MutPred

0.41

Loss of catalytic residue at P66 (P = 0.0216);

MVP

0.60

MPC

2.1

ClinPred

1.0

GERP RS

5.3

Varity_R

0.18

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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