dbSNP rs779233476: KRTAP5-4:p.Gly20Ser (chr11-1622036-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001347674.1(KRTAP5-4):c.58G>A(p.Gly20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,355,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

KRTAP5-4
NM_001347674.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

Publications

2 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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028504133).

BP6

Variant 11-1622036-C-T is Benign according to our data. Variant chr11-1622036-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3117108.Status of the report is criteria_provided_single_submitter, 1 stars.

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.58G>A	p.Gly20Ser	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.58G>A	p.Gly20Ser	missense	Exon 1 of 1	ENSP00000382590.1	A8MUN0

Frequencies

GnomAD3 genomes

AF:

0.0000387

AC:

AN:

129140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000582

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:

0.00435

Gnomad NFE

AF:

0.0000340

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000333

AC:

AN:

239992

AF XY:

0.0000229

show subpopulations

Gnomad AFR exome

AF:

0.000143

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000163

AC:

AN:

1226128

Hom.:

Cov.:

AF XY:

0.00000983

AC XY:

AN XY:

610382

show subpopulations

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

African (AFR)

AF:

0.0000729

AC:

AN:

27428

American (AMR)

AF:

0.000104

AC:

AN:

38374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21274

East Asian (EAS)

AF:

0.00

AC:

AN:

29964

South Asian (SAS)

AF:

0.0000269

AC:

AN:

74358

European-Finnish (FIN)

AF:

0.0000438

AC:

AN:

45696

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3906

European-Non Finnish (NFE)

AF:

0.0000107

AC:

AN:

935164

Other (OTH)

AF:

0.00

AC:

AN:

49964

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000241704), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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:

0.0000387

AC:

AN:

129228

Hom.:

Cov.:

AF XY:

0.0000475

AC XY:

AN XY:

63210

show subpopulations

African (AFR)

AF:

0.0000581

AC:

AN:

34436

American (AMR)

AF:

0.00

AC:

AN:

13202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2928

East Asian (EAS)

AF:

0.00

AC:

AN:

3922

South Asian (SAS)

AF:

0.00

AC:

AN:

3866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9248

Middle Eastern (MID)

AF:

0.00459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000340

AC:

AN:

58858

Other (OTH)

AF:

0.00

AC:

AN:

1778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.00

Hom.:

ExAC

AF:

0.0000356

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.061

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

(source)

DANN

Benign

0.53

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0062

M_CAP

Benign

0.0028

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.95

PhyloP100

-1.6

PROVEAN

Benign

2.0

REVEL

Benign

0.030

Sift

Pathogenic

0.0

Sift4G

Benign

0.67

Vest4

0.052

MutPred

0.16

Gain of phosphorylation at G20 (P = 0.026)

MVP

0.030

MPC

0.026

ClinPred

0.021

GERP RS

-3.8

PromoterAI

-0.0077

Neutral

(source)

gMVP

0.017

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