Genetic Variant KRTAP2-3:p.Val104Leu (chr17-41059741-C-G) – 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.310G>C(p.Val104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,552,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. V104M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

KRTAP2-3
NM_001165252.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23278183).

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.310G>C	p.Val104Leu	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.310G>C	p.Val104Leu	missense	Exon 1 of 1	ENSP00000375237.2	P0C7H8
ENSG00000306126	ENST00000815522.1		n.214C>G		non_coding_transcript_exon	Exon 1 of 2
ENSG00000306126	ENST00000815517.1		n.220-558C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00000645

AC:

AN:

155084

AF XY:

0.0000122

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1400794

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691068

show subpopulations

African (AFR)

AF:

0.0000311

AC:

AN:

32104

American (AMR)

AF:

0.00

AC:

AN:

35850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25186

East Asian (EAS)

AF:

0.00

AC:

AN:

36486

South Asian (SAS)

AF:

0.00

AC:

AN:

79362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4518

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080728

Other (OTH)

AF:

0.00

AC:

AN:

58006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000132

AC:

AN:

151782

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41376

American (AMR)

AF:

0.00

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67924

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0025

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.52

M_CAP

Benign

0.0051

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.6

PhyloP100

1.9

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.90

REVEL

Benign

0.14

Sift

Benign

0.050

Sift4G

Uncertain

0.037

Vest4

0.30

MutPred

0.56

Gain of catalytic residue at Q100 (P = 0.1574)

MVP

0.20

MPC

2.2

ClinPred

0.75

GERP RS

4.7

PromoterAI

0.010

Neutral

(source)

Varity_R

0.084

gMVP

0.068

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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