Genetic Variant KRTAP2-3:p.Arg75His (chr17-41059827-C-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_001165252.2(KRTAP2-3):c.224G>A(p.Arg75His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,382,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R75L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP2-3
NM_001165252.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.847

Publications

0 publications found

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:

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=0.2249614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165252.2. 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
	KRTAP2-3	NM_001165252.2	MANE Select	c.224G>A	p.Arg75His	missense	Exon 1 of 1	NP_001158724.1	P0C7H8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP2-3	ENST00000391418.3	TSL:6 MANE Select	c.224G>A	p.Arg75His	missense	Exon 1 of 1	ENSP00000375237.2	P0C7H8
ENSG00000306126	ENST00000815517.1		n.220-472C>T		intron	N/A
ENSG00000306126	ENST00000815518.1		n.160-472C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151462

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

GnomAD2 exomes

AF:

0.00000768

AC:

AN:

130218

AF XY:

0.0000143

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000413

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1382188

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

681018

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31426

American (AMR)

AF:

0.0000281

AC:

AN:

35566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25044

East Asian (EAS)

AF:

0.00

AC:

AN:

35606

South Asian (SAS)

AF:

0.00

AC:

AN:

78974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4046

European-Non Finnish (NFE)

AF:

0.00000279

AC:

AN:

1075134

Other (OTH)

AF:

0.00

AC:

AN:

57526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

151580

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74064

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67796

Other (OTH)

AF:

0.00

AC:

AN:

2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.080

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.061

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.035

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

PhyloP100

0.85

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.081

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.028

Vest4

0.18

MutPred

0.67

Gain of glycosylation at T78 (P = 0.0688)

MVP

0.23

MPC

2.5

ClinPred

0.72

GERP RS

2.3

PromoterAI

0.023

Neutral

(source)

Varity_R

0.079

gMVP

0.075

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over