Genetic Variant KRTAP2-1:p.Arg52His (chr17-41047113-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001123387.1(KRTAP2-1):c.155G>A(p.Arg52His) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP2-1
NM_001123387.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

Publications

0 publications found

Variant links:

Genes affected

KRTAP2-1 (HGNC:16775): (keratin associated protein 2-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP2-1 links:

ENSG00000306126 (HGNC:):

ENSG00000306126 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36765766).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123387.1. 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
	KRTAP2-1	NM_001123387.1	MANE Select	c.155G>A	p.Arg52His	missense	Exon 1 of 1	NP_001116859.1	Q9BYU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP2-1	ENST00000391419.3	TSL:6 MANE Select	c.155G>A	p.Arg52His	missense	Exon 1 of 1	ENSP00000375238.3	Q9BYU5
ENSG00000306126	ENST00000815517.1		n.220-13186C>T		intron	N/A
ENSG00000306126	ENST00000815518.1		n.160-13186C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000530

AC:

AN:

150874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000732

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:

0.0000739

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000461

AC:

AN:

65112

AF XY:

0.0000304

show subpopulations

Gnomad AFR exome

AF:

0.000176

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000832

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000210

AC:

AN:

1187826

Hom.:

Cov.:

AF XY:

0.0000241

AC XY:

AN XY:

581300

show subpopulations

African (AFR)

AF:

0.0000750

AC:

AN:

26680

American (AMR)

AF:

0.00

AC:

AN:

23008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18596

East Asian (EAS)

AF:

0.00

AC:

AN:

34460

South Asian (SAS)

AF:

0.00

AC:

AN:

61290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3456

European-Non Finnish (NFE)

AF:

0.0000245

AC:

AN:

939894

Other (OTH)

AF:

0.00

AC:

AN:

50220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000530

AC:

AN:

150874

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73574

show subpopulations

African (AFR)

AF:

0.0000732

AC:

AN:

40992

American (AMR)

AF:

0.00

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000739

AC:

AN:

67668

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000741

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.036

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.012

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.8

PhyloP100

4.5

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.32

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.060

Polyphen

1.0

Vest4

0.30

MutPred

0.56

Gain of catalytic residue at R52 (P = 0.0435)

MVP

0.31

ClinPred

0.52

GERP RS

5.8

PromoterAI

0.020

Neutral

(source)

Varity_R

0.32

gMVP

0.074

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over