Genetic Variant KRTAP5-10:p.Cys104Tyr (chr11-71565898-G-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_001012710.2(KRTAP5-10):c.311G>A(p.Cys104Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,402,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

KRTAP5-10
NM_001012710.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.563

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:

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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=0.0856331).

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.311G>A	p.Cys104Tyr	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.311G>A	p.Cys104Tyr	missense	Exon 1 of 1	ENSP00000381542.1	Q6L8G5

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

137350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000721

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:

0.000222

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000903

AC:

AN:

243656

AF XY:

0.0000681

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:

0.000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000194

AC:

245

AN:

1265198

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

118

AN XY:

626748

show subpopulations

African (AFR)

AF:

0.0000360

AC:

AN:

27752

American (AMR)

AF:

0.00

AC:

AN:

34752

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21976

East Asian (EAS)

AF:

0.00

AC:

AN:

30078

South Asian (SAS)

AF:

0.0000131

AC:

AN:

76350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3538

European-Non Finnish (NFE)

AF:

0.000241

AC:

236

AN:

977550

Other (OTH)

AF:

0.000137

AC:

AN:

51070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

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:

0.000116

AC:

AN:

137350

Hom.:

Cov.:

AF XY:

0.0000752

AC XY:

AN XY:

66530

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000275

AC:

AN:

36398

American (AMR)

AF:

0.0000721

AC:

AN:

13876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3284

East Asian (EAS)

AF:

0.00

AC:

AN:

4508

South Asian (SAS)

AF:

0.00

AC:

AN:

3708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000222

AC:

AN:

63124

Other (OTH)

AF:

0.00

AC:

AN:

1850

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000248983), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.381

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:

0.000119

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000499

AC:

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

0.26

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.058

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.56

M_CAP

Benign

0.0023

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.7

PhyloP100

0.56

PROVEAN

Benign

-1.7

REVEL

Benign

0.073

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.33

Vest4

0.15

MVP

0.067

MPC

0.0078

ClinPred

0.17

GERP RS

1.9

PromoterAI

0.021

Neutral

(source)

Varity_R

0.40

gMVP

0.040

Mutation Taster

=97/3

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