Genetic Variant KRTAP5-1:p.Cys69Tyr (chr11-1585044-C-T) – 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_001005922.1(KRTAP5-1):c.206G>A(p.Cys69Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000053 in 1,604,244 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 0.00019 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

KRTAP5-1
NM_001005922.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

Publications

1 publications found

Variant links:

Genes affected

KRTAP5-1 (HGNC:23596): (keratin associated protein 5-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-1 links:

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

KRTAP5-AS1 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=0.12793887).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005922.1. 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
	KRTAP5-1	NM_001005922.1	MANE Select	c.206G>A	p.Cys69Tyr	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11976C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP5-1	ENST00000382171.2	TSL:6 MANE Select	c.206G>A	p.Cys69Tyr	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11976C>T		intron	N/A
KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12204C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

145770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000694

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:

0.0000439

AC:

AN:

250742

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000684

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:

0.0000398

AC:

AN:

1458360

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

725518

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

33312

American (AMR)

AF:

0.00

AC:

AN:

44258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.00

AC:

AN:

86038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.000438

AC:

AN:

4570

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111056

Other (OTH)

AF:

0.000116

AC:

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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:

0.000185

AC:

AN:

145884

Hom.:

Cov.:

AF XY:

0.000141

AC XY:

AN XY:

71018

show subpopulations

African (AFR)

AF:

0.000692

AC:

AN:

39044

American (AMR)

AF:

0.00

AC:

AN:

14486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

4858

South Asian (SAS)

AF:

0.00

AC:

AN:

4442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66456

Other (OTH)

AF:

0.00

AC:

AN:

1988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000425

Hom.:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

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

0.20

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.14

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.14

M_CAP

Benign

0.0030

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

PhyloP100

4.1

PROVEAN

Benign

-1.5

REVEL

Benign

0.068

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.024

Polyphen

0.99

Vest4

0.44

MVP

0.22

MPC

0.060

ClinPred

0.19

GERP RS

2.9

PromoterAI

0.017

Neutral

(source)

Varity_R

0.72

gMVP

0.11

Mutation Taster

=83/17

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