Genetic Variant NM_033032.3:c.65C>G (chr17-41055147-G-C) – 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.65C>G(p.Pro22Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000604 in 1,374,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

KRTAP2-2
NM_033032.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18

Publications

1 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:

Genome browser will be placed here

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=0.17038432).

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.65C>G	p.Pro22Arg	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.65C>G	p.Pro22Arg	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
ENSG00000306126	ENST00000815517.1		n.220-5152G>C		intron	N/A
ENSG00000306126	ENST00000815518.1		n.160-5152G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000563

AC:

AN:

142092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000714

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:

0.0000768

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000106

AC:

AN:

75534

AF XY:

0.000130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.000405

GnomAD4 exome

AF:

0.0000609

AC:

AN:

1231978

Hom.:

Cov.:

AF XY:

0.0000630

AC XY:

AN XY:

603136

show subpopulations

African (AFR)

AF:

0.0000730

AC:

AN:

27380

American (AMR)

AF:

0.000161

AC:

AN:

24918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19432

East Asian (EAS)

AF:

0.0000574

AC:

AN:

34858

South Asian (SAS)

AF:

0.0000927

AC:

AN:

64752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3546

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

973992

Other (OTH)

AF:

0.000115

AC:

AN:

52008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

AF:

0.0000563

AC:

AN:

142204

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

68870

show subpopulations

African (AFR)

AF:

0.0000526

AC:

AN:

38006

American (AMR)

AF:

0.0000713

AC:

AN:

14032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3374

East Asian (EAS)

AF:

0.00

AC:

AN:

4996

South Asian (SAS)

AF:

0.00

AC:

AN:

4088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000768

AC:

AN:

65122

Other (OTH)

AF:

0.00

AC:

AN:

1896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000193

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

0.28

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.71

M_CAP

Benign

0.0083

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.68

MutationAssessor

Pathogenic

3.1

PhyloP100

4.2

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Vest4

0.32

MutPred

0.57

Loss of catalytic residue at P22 (P = 0.1203)

MVP

0.43

ClinPred

0.27

GERP RS

5.2

PromoterAI

0.00060

Neutral

(source)

Varity_R

0.68

gMVP

0.091

Mutation Taster

=50/50

(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