Genetic Variant KRTAP2-3:p.Cys46Phe (chr17-41059914-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001165252.2(KRTAP2-3):c.137G>T(p.Cys46Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000085 in 1,505,434 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000091 ( 1 hom. )

Consequence

KRTAP2-3
NM_001165252.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30726796).

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.137G>T	p.Cys46Phe	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.137G>T	p.Cys46Phe	missense	Exon 1 of 1	ENSP00000375237.2	P0C7H8
ENSG00000306126	ENST00000815517.1		n.220-385C>A		intron	N/A
ENSG00000306126	ENST00000815518.1		n.160-385C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

151280

Hom.:

Cov.:

show subpopulations

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:

0.0000738

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000594

AC:

AN:

84224

AF XY:

0.0000922

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000161

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000908

AC:

123

AN:

1354154

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

664288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31148

American (AMR)

AF:

0.00

AC:

AN:

34024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23006

East Asian (EAS)

AF:

0.00

AC:

AN:

35442

South Asian (SAS)

AF:

0.00

AC:

AN:

74300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3918

European-Non Finnish (NFE)

AF:

0.000115

AC:

122

AN:

1062710

Other (OTH)

AF:

0.0000177

AC:

AN:

56472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000331

AC:

AN:

151280

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73840

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41266

American (AMR)

AF:

0.00

AC:

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000738

AC:

AN:

67718

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.0000875

Hom.:

Bravo

AF:

0.0000340

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

-0.24

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.00048

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.60

M_CAP

Benign

0.018

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

PhyloP100

2.5

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-9.9

REVEL

Benign

0.18

Sift

Benign

0.063

Sift4G

Uncertain

0.010

Vest4

0.35

MutPred

0.43

Loss of glycosylation at T45 (P = 0.1309)

MVP

0.38

MPC

1.6

ClinPred

0.66

GERP RS

3.6

PromoterAI

0.038

Neutral

(source)

Varity_R

0.24

gMVP

0.31

Mutation Taster

=84/16

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over