Genetic Variant KRTAP21-3:p.Phe51Tyr (chr21-30718608-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164435.1(KRTAP21-3):c.152T>A(p.Phe51Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000281 in 1,531,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

KRTAP21-3
NM_001164435.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.813

Publications

1 publications found

Variant links:

Genes affected

KRTAP21-3 (HGNC:34216): (keratin associated protein 21-3) Predicted to be located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP21-3 links:

ENSG00000295670 (HGNC:):

ENSG00000295670 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0412499).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164435.1. 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
	KRTAP21-3	NM_001164435.1	MANE Select	c.152T>A	p.Phe51Tyr	missense	Exon 1 of 1	NP_001157907.1	Q3LHN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP21-3	ENST00000444335.1	TSL:6 MANE Select	c.152T>A	p.Phe51Tyr	missense	Exon 1 of 1	ENSP00000404517.1	Q3LHN1
	ENSG00000295670	ENST00000731715.1		n.137+6909T>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000397

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000192

AC:

AN:

135186

AF XY:

0.000182

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.000539

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.000539

GnomAD4 exome

AF:

0.000285

AC:

393

AN:

1379058

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

189

AN XY:

679618

show subpopulations

African (AFR)

AF:

0.0000658

AC:

AN:

30410

American (AMR)

AF:

0.000682

AC:

AN:

30770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24466

East Asian (EAS)

AF:

0.00

AC:

AN:

34780

South Asian (SAS)

AF:

0.00

AC:

AN:

74636

European-Finnish (FIN)

AF:

0.0000407

AC:

AN:

49128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.000333

AC:

357

AN:

1072062

Other (OTH)

AF:

0.000192

AC:

AN:

57202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000243

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41586

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.000267

Hom.:

Bravo

AF:

0.000249

ExAC

AF:

0.000162

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

0.14

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.5

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.058

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.13

M_CAP

Benign

0.0015

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.90

PhyloP100

-0.81

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.11

Vest4

0.14

MVP

0.030

ClinPred

0.029

GERP RS

-5.0

PromoterAI

0.0020

Neutral

(source)

Varity_R

0.39

gMVP

0.0024

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

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