Genetic Variant NM_052904.4:c.753C>T (chr6-97113908-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_052904.4(KLHL32):c.753C>T(p.Val251Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,614,062 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 95 hom. )

Consequence

KLHL32
NM_052904.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0150

Publications

3 publications found

Variant links:

Genes affected

KLHL32 (HGNC:21221): (kelch like family member 32)

KLHL32 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00380975).

BP6

Variant 6-97113908-C-T is Benign according to our data. Variant chr6-97113908-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656778.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.015 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052904.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLHL32	NM_052904.4	MANE Select	c.753C>T	p.Val251Val	synonymous	Exon 7 of 11	NP_443136.2	Q96NJ5-1
KLHL32	NM_001323256.2		c.832C>T	p.Pro278Ser	missense	Exon 8 of 8	NP_001310185.1
KLHL32	NM_001323252.2		c.753C>T	p.Val251Val	synonymous	Exon 8 of 12	NP_001310181.1	Q96NJ5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLHL32	ENST00000369261.9	TSL:2 MANE Select	c.753C>T	p.Val251Val	synonymous	Exon 7 of 11	ENSP00000358265.4	Q96NJ5-1
KLHL32	ENST00000620278.1	TSL:1	c.-38-13496C>T		intron	N/A	ENSP00000482012.1	A0A087WYQ8
KLHL32	ENST00000447886.1	TSL:3	c.520C>T	p.Pro174Ser	missense	Exon 4 of 4	ENSP00000389310.1	Q5THS9

Frequencies

GnomAD3 genomes

AF:

0.00700

AC:

1065

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0558

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00587

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00778

AC:

1955

AN:

251378

AF XY:

0.00768

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0510

Gnomad NFE exome

AF:

0.00640

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.00634

AC:

9263

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

4448

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33480

American (AMR)

AF:

0.000738

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000974

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0471

AC:

2514

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00560

AC:

6232

AN:

1112006

Other (OTH)

AF:

0.00621

AC:

375

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

616

1233

1849

2466

3082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

224

448

672

896

1120

<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:

0.00700

AC:

1065

AN:

152180

Hom.:

Cov.:

AF XY:

0.00864

AC XY:

643

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41530

American (AMR)

AF:

0.00105

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00269

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0558

AC:

590

AN:

10572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00587

AC:

399

AN:

68020

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

167

222

278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00290

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00731

AC:

888

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00474

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

1.7

(source)

DANN

Benign

0.62

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.1

PhyloP100

0.015

PROVEAN

Benign

0.68

REVEL

Benign

0.017

Sift

Pathogenic

0.0

MVP

0.36

ClinPred

0.032

GERP RS

1.2

Mutation Taster

=80/20

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