Genetic Variant KRTAP2-2:p.Pro113Thr (chr17-41054875-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033032.3(KRTAP2-2):c.337C>A(p.Pro113Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P113A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 15)

Failed GnomAD Quality Control

Consequence

KRTAP2-2
NM_033032.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

Publications

0 publications found

Variant links:

Genes affected

KRTAP2-2 (HGNC:18905): (keratin associated protein 2-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP2-2 links:

ENSG00000306126 (HGNC:):

ENSG00000306126 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15443647).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033032.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-2	NM_033032.3	MANE Select	c.337C>A	p.Pro113Thr	missense	Exon 1 of 1	NP_149021.2	Q9BYT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP2-2	ENST00000398477.1	TSL:6 MANE Select	c.337C>A	p.Pro113Thr	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
ENSG00000306126	ENST00000815517.1		n.220-5424G>T		intron	N/A
ENSG00000306126	ENST00000815518.1		n.160-5424G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

96062

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

96062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

45946

African (AFR)

AF:

0.00

AC:

AN:

14590

American (AMR)

AF:

0.00

AC:

AN:

9544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2884

East Asian (EAS)

AF:

0.00

AC:

AN:

3460

South Asian (SAS)

AF:

0.00

AC:

AN:

2906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53068

Other (OTH)

AF:

0.00

AC:

AN:

1320

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.3

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.52

M_CAP

Benign

0.0093

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.0

PhyloP100

1.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.78

REVEL

Benign

0.16

Sift

Benign

0.28

Sift4G

Benign

0.23

Vest4

0.29

MutPred

0.34

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.072

ClinPred

0.12

GERP RS

2.7

PromoterAI

0.0094

Neutral

(source)

Varity_R

0.039

gMVP

0.047

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over