Genetic Variant KRTAP5-4:p.Val63Leu (chr11-1621907-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001347674.1(KRTAP5-4):c.187G>T(p.Val63Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,603,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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. V63M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000096 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

KRTAP5-4
NM_001347674.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.238

Publications

1 publications found

Variant links:

Genes affected

KRTAP5-4 (HGNC:23599): (keratin associated protein 5-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08258432).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347674.1. 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
	KRTAP5-4	NM_001347674.1	MANE Select	c.187G>T	p.Val63Leu	missense	Exon 1 of 1	NP_001334603.1	A8MUN0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-4	ENST00000399682.1	TSL:6 MANE Select	c.187G>T	p.Val63Leu	missense	Exon 1 of 1	ENSP00000382590.1	A8MUN0

Frequencies

GnomAD3 genomes

AF:

0.0000956

AC:

AN:

146448

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000957

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:

0.0000520

AC:

AN:

249854

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

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:

0.00000961

AC:

AN:

1457496

Hom.:

Cov.:

117

AF XY:

0.00000689

AC XY:

AN XY:

725188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33278

American (AMR)

AF:

0.000314

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25988

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

86158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4482

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110048

Other (OTH)

AF:

0.00

AC:

AN:

60020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000956

AC:

AN:

146448

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

AN XY:

71190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39276

American (AMR)

AF:

0.000957

AC:

AN:

14634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

4760

South Asian (SAS)

AF:

0.00

AC:

AN:

4460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66880

Other (OTH)

AF:

0.00

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.0023

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

PhyloP100

-0.24

PROVEAN

Benign

-0.010

REVEL

Benign

0.086

Sift

Pathogenic

0.0

Sift4G

Benign

0.63

Vest4

0.38

MutPred

0.22

Gain of phosphorylation at S67 (P = 0.358)

MVP

0.29

MPC

0.026

ClinPred

0.16

GERP RS

3.3

PromoterAI

-0.0027

Neutral

(source)

gMVP

0.031

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over