Genetic Variant NM_001012710.2:c.152C>G (chr11-71565739-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001012710.2(KRTAP5-10):c.152C>G(p.Pro51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000908 in 1,608,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

KRTAP5-10
NM_001012710.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.71

Publications

0 publications found

Variant links:

Genes affected

KRTAP5-10 (HGNC:23605): (keratin associated protein 5-10) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-10 links:

ENSG00000286948 (HGNC:):

ENSG00000286948 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057454705).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012710.2. 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
	KRTAP5-10	NM_001012710.2	MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 1 of 1	NP_001012728.1	Q6L8G5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-10	ENST00000398531.3	TSL:6 MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 1 of 1	ENSP00000381542.1	Q6L8G5
	ENSG00000286948	ENST00000661699.1		n.-131G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.000208

AC:

AN:

148792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0210

Gnomad AMR

AF:

0.000135

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:

0.000134

Gnomad OTH

AF:

0.000490

GnomAD2 exomes

AF:

0.0000641

AC:

AN:

249580

AF XY:

0.0000887

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:

0.000133

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000788

AC:

115

AN:

1459914

Hom.:

Cov.:

123

AF XY:

0.0000730

AC XY:

AN XY:

726248

show subpopulations

African (AFR)

AF:

0.0000898

AC:

AN:

33408

American (AMR)

AF:

0.0000448

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.000210

AC:

AN:

4754

European-Non Finnish (NFE)

AF:

0.0000918

AC:

102

AN:

1111530

Other (OTH)

AF:

0.0000996

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000208

AC:

AN:

148792

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

AN XY:

72414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40228

American (AMR)

AF:

0.000135

AC:

AN:

14864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4900

South Asian (SAS)

AF:

0.00

AC:

AN:

4640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000134

AC:

AN:

67344

Other (OTH)

AF:

0.000490

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.000203

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000256

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

0.27

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.14

Eigen

Benign

-0.017

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.29

M_CAP

Benign

0.00099

MetaRNN

Benign

0.0057

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.7

PhyloP100

-1.7

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.045

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.037

Polyphen

0.93

Vest4

0.10

MVP

0.21

MPC

0.0085

ClinPred

0.23

GERP RS

1.8

PromoterAI

-0.0064

Neutral

(source)

Varity_R

0.19

gMVP

0.12

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

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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