Genetic Variant HOMEZ:p.Thr56Thr (chr14-23277060-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020834.3(HOMEZ):c.168G>C(p.Thr56Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,613,728 control chromosomes in the GnomAD database, including 40,760 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3185 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37575 hom. )

Consequence

HOMEZ
NM_020834.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200

Publications

17 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=0.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMEZ	NM_020834.3 link	c.168G>C	p.Thr56Thr	synonymous_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.168G>C	p.Thr56Thr	synonymous_variant	Exon 2 of 2	1	NM_020834.3	ENSP00000350049.4	Q8IX15-1
HOMEZ	ENST00000561013.3 link	c.174G>C	p.Thr58Thr	synonymous_variant	Exon 3 of 3	2		ENSP00000453979.1	Q8IX15-3
HOMEZ	ENST00000673724.1 link	c.168G>C	p.Thr56Thr	synonymous_variant	Exon 2 of 3			ENSP00000501153.1	A0A669KB72
HOMEZ	ENST00000606731.2 link	c.-115G>C		upstream_gene_variant		2		ENSP00000475307.3	U3KPW8

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29817

AN:

152002

Hom.:

3181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.216

GnomAD2 exomes

AF:

0.206

AC:

51165

AN:

248954

AF XY:

0.207

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.223

AC:

326552

AN:

1461608

Hom.:

37575

Cov.:

AF XY:

0.222

AC XY:

161622

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.122

AC:

4078

AN:

33480

American (AMR)

AF:

0.201

AC:

9001

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5504

AN:

26134

East Asian (EAS)

AF:

0.169

AC:

6724

AN:

39700

South Asian (SAS)

AF:

0.179

AC:

15480

AN:

86254

European-Finnish (FIN)

AF:

0.246

AC:

13114

AN:

53398

Middle Eastern (MID)

AF:

0.184

AC:

1063

AN:

5768

European-Non Finnish (NFE)

AF:

0.233

AC:

258842

AN:

1111788

Other (OTH)

AF:

0.211

AC:

12746

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

14742

29484

44226

58968

73710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8898

17796

26694

35592

44490

<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:

0.196

AC:

29837

AN:

152120

Hom.:

3185

Cov.:

AF XY:

0.197

AC XY:

14626

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.126

AC:

5210

AN:

41504

American (AMR)

AF:

0.225

AC:

3442

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

732

AN:

3472

East Asian (EAS)

AF:

0.160

AC:

826

AN:

5158

South Asian (SAS)

AF:

0.192

AC:

924

AN:

4822

European-Finnish (FIN)

AF:

0.256

AC:

2706

AN:

10578

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15320

AN:

67972

Other (OTH)

AF:

0.220

AC:

465

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1214

2427

3641

4854

6068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.129

Hom.:

326

Bravo

AF:

0.189

Asia WGS

AF:

0.191

AC:

661

AN:

3478

EpiCase

AF:

0.226

EpiControl

AF:

0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.0

(source)

DANN

Benign

0.74

PhyloP100

0.020

PromoterAI

0.0084

Neutral

(source)

Mutation Taster

=90/10

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