Genetic Variant KRTAP24-1:p.Val112Ile (chr21-30282599-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001085455.3(KRTAP24-1):c.334G>A(p.Val112Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,588,650 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

KRTAP24-1
NM_001085455.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.24

Publications

3 publications found

Variant links:

Genes affected

KRTAP24-1 (HGNC:33902): (keratin associated protein 24-1) Predicted to enable structural molecule activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP24-1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007895142).

BP6

Variant 21-30282599-C-T is Benign according to our data. Variant chr21-30282599-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2287380.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085455.3. 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
	KRTAP24-1	NM_001085455.3	MANE Select	c.334G>A	p.Val112Ile	missense	Exon 1 of 1	NP_001078924.1	Q3LI83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP24-1	ENST00000340345.6	TSL:6 MANE Select	c.334G>A	p.Val112Ile	missense	Exon 1 of 1	ENSP00000339238.4	Q3LI83

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000270

AC:

AN:

225834

AF XY:

0.000322

show subpopulations

Gnomad AFR exome

AF:

0.000458

Gnomad AMR exome

AF:

0.000461

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000675

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000121

AC:

174

AN:

1436562

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

122

AN XY:

711710

show subpopulations

African (AFR)

AF:

0.000273

AC:

AN:

32954

American (AMR)

AF:

0.000373

AC:

AN:

42844

Ashkenazi Jewish (ASJ)

AF:

0.0000418

AC:

AN:

23902

East Asian (EAS)

AF:

0.0000759

AC:

AN:

39542

South Asian (SAS)

AF:

0.00133

AC:

107

AN:

80568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52096

Middle Eastern (MID)

AF:

0.000356

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.0000255

AC:

AN:

1099710

Other (OTH)

AF:

0.000135

AC:

AN:

59334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000256

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41488

American (AMR)

AF:

0.00124

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5144

South Asian (SAS)

AF:

0.000832

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.0000548

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000477

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000240

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.063

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.010

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.00063

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.30

M_CAP

Benign

0.0013

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.2

PhyloP100

-1.2

PrimateAI

Benign

0.27

PROVEAN

Benign

0.45

REVEL

Benign

0.0040

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.025

MVP

0.076

MPC

0.013

ClinPred

0.012

GERP RS

-6.6

PromoterAI

-0.068

Neutral

(source)

Varity_R

0.020

gMVP

0.033

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