Genetic Variant HOMEZ:p.Ala302Thr (chr14-23276324-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020834.3(HOMEZ):c.904G>A(p.Ala302Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,613,070 control chromosomes in the GnomAD database, including 133,528 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12233 hom., cov: 31)

Exomes 𝑓: 0.41 ( 121295 hom. )

Consequence

HOMEZ
NM_020834.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.136

Publications

31 publications found

Variant links:

Genes affected

HOMEZ (HGNC:20164): (homeobox and leucine zipper encoding) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

HOMEZ links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0027455986).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMEZ	NM_020834.3 link	c.904G>A	p.Ala302Thr	missense_variant	Exon 2 of 2	ENST00000357460.7	NP_065885.2	Q8IX15-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HOMEZ	ENST00000357460.7 link	c.904G>A	p.Ala302Thr	missense_variant	Exon 2 of 2	1	NM_020834.3	ENSP00000350049.4	Q8IX15-1
HOMEZ	ENST00000561013.3 link	c.910G>A	p.Ala304Thr	missense_variant	Exon 3 of 3	2		ENSP00000453979.1	Q8IX15-3
HOMEZ	ENST00000673724.1 link	c.571G>A	p.Ala191Thr	missense_variant	Exon 3 of 3			ENSP00000501153.1	A0A669KB72
HOMEZ	ENST00000606731.2 link	c.394G>A	p.Ala132Thr	missense_variant	Exon 2 of 2	2		ENSP00000475307.3	U3KPW8

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60478

AN:

151738

Hom.:

12228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.395

GnomAD2 exomes

AF:

0.382

AC:

94692

AN:

248176

AF XY:

0.388

show subpopulations

Gnomad AFR exome

AF:

0.399

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.382

GnomAD4 exome

AF:

0.405

AC:

592262

AN:

1461212

Hom.:

121295

Cov.:

AF XY:

0.405

AC XY:

294546

AN XY:

726860

show subpopulations

African (AFR)

AF:

0.396

AC:

13255

AN:

33480

American (AMR)

AF:

0.258

AC:

11502

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

11381

AN:

26110

East Asian (EAS)

AF:

0.352

AC:

13965

AN:

39696

South Asian (SAS)

AF:

0.365

AC:

31443

AN:

86232

European-Finnish (FIN)

AF:

0.415

AC:

22151

AN:

53380

Middle Eastern (MID)

AF:

0.464

AC:

2676

AN:

5768

European-Non Finnish (NFE)

AF:

0.415

AC:

461490

AN:

1111532

Other (OTH)

AF:

0.404

AC:

24399

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

20934

41869

62803

83738

104672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14018

28036

42054

56072

70090

<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:

0.398

AC:

60500

AN:

151858

Hom.:

12233

Cov.:

AF XY:

0.396

AC XY:

29354

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.396

AC:

16402

AN:

41392

American (AMR)

AF:

0.306

AC:

4674

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

1506

AN:

3472

East Asian (EAS)

AF:

0.321

AC:

1656

AN:

5154

South Asian (SAS)

AF:

0.348

AC:

1675

AN:

4812

European-Finnish (FIN)

AF:

0.418

AC:

4393

AN:

10522

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.425

AC:

28870

AN:

67938

Other (OTH)

AF:

0.394

AC:

829

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1850

3699

5549

7398

9248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.416

Hom.:

35722

Bravo

AF:

0.390

TwinsUK

AF:

0.424

AC:

1573

ALSPAC

AF:

0.418

AC:

1612

ESP6500AA

AF:

0.379

AC:

1556

ESP6500EA

AF:

0.429

AC:

3585

ExAC

AF:

0.388

AC:

46867

EpiCase

AF:

0.427

EpiControl

AF:

0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.00022

T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.2

N;.;.

PhyloP100

-0.14

PrimateAI

Benign

0.27

PROVEAN

Benign

0.87

N;N;.

REVEL

Benign

0.032

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.0090

MPC

0.23

ClinPred

0.0031

GERP RS

-2.6

Varity_R

0.030

gMVP

0.19

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over