dbSNP rs77039648: KRTAP5-5:p.Tyr192Cys (chr11-1630415-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001001480.3(KRTAP5-5):c.575A>G(p.Tyr192Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP5-5
NM_001001480.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.02

Publications

15 publications found

Variant links:

Genes affected

KRTAP5-5 (HGNC:23601): (keratin associated protein 5-5) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017537773).

BP6

Variant 11-1630415-A-G is Benign according to our data. Variant chr11-1630415-A-G is described in ClinVar as [Benign]. Clinvar id is 403024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-5	NM_001001480.3 link	c.575A>G	p.Tyr192Cys	missense_variant	Exon 1 of 1	ENST00000399676.4	NP_001001480.2	Q701N2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-5	ENST00000399676.4 link	c.575A>G	p.Tyr192Cys	missense_variant	Exon 1 of 1	6	NM_001001480.3	ENSP00000382584.2		Q701N2

Frequencies

GnomAD3 genomes

AF:

0.0000375

AC:

AN:

26668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000171

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:

0.00535

AC:

204

AN:

38148

AF XY:

0.00658

show subpopulations

Gnomad AFR exome

AF:

0.00217

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.00543

Gnomad EAS exome

AF:

0.00287

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.00955

Gnomad OTH exome

AF:

0.00731

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000167

AC:

AN:

599412

Hom.:

Cov.:

AF XY:

0.00000333

AC XY:

AN XY:

299886

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

12198

American (AMR)

AF:

0.00

AC:

AN:

22342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11544

East Asian (EAS)

AF:

0.00

AC:

AN:

20904

South Asian (SAS)

AF:

0.00

AC:

AN:

36144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2174

European-Non Finnish (NFE)

AF:

0.00000224

AC:

AN:

445476

Other (OTH)

AF:

0.00

AC:

AN:

25202

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.075

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000375

AC:

AN:

26670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

13096

show subpopulations

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

African (AFR)

AF:

0.000170

AC:

AN:

5866

American (AMR)

AF:

0.00

AC:

AN:

3100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

644

East Asian (EAS)

AF:

0.00

AC:

AN:

1784

South Asian (SAS)

AF:

0.00

AC:

AN:

850

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

12136

Other (OTH)

AF:

0.00

AC:

AN:

360

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0471

Hom.:

ExAC

AF:

0.176

AC:

20322

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Does not pass quality filter -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.9

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.000064

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0023

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.7

PhyloP100

1.0

PROVEAN

Benign

2.2

REVEL

Benign

0.040

Sift

Benign

0.17

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.066

MPC

0.24

ClinPred

0.0024

GERP RS

0.95

Varity_R

0.042

gMVP

0.058

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over