Variant chr14-23276324-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HOMEZ	NM_020834.3 linkuse as main transcript	c.904G>A	p.Ala302Thr	missense_variant	2/2	ENST00000357460.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMEZ	ENST00000357460.7 linkuse as main transcript	c.904G>A	p.Ala302Thr	missense_variant	2/2	1	NM_020834.3	P2	Q8IX15-1
HOMEZ	ENST00000561013.3 linkuse as main transcript	c.910G>A	p.Ala304Thr	missense_variant	3/3	2		A2	Q8IX15-3
HOMEZ	ENST00000673724.1 linkuse as main transcript	c.571G>A	p.Ala191Thr	missense_variant	3/3			A2
HOMEZ	ENST00000606731.2 linkuse as main transcript	c.394G>A	p.Ala132Thr	missense_variant	2/2	2

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

GnomAD3 exomes

AF:

0.382

AC:

94692

AN:

248176

Hom.:

18616

AF XY:

0.388

AC XY:

52181

AN XY:

134616

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 SAS exome

AF:

0.358

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

Gnomad4 AFR exome

AF:

0.396

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.352

Gnomad4 SAS exome

AF:

0.365

Gnomad4 FIN exome

AF:

0.415

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.404

GnomAD4 genome

AF:

0.398

AC:

60500

AN:

151858

Hom.:

12233

Cov.:

AF XY:

0.396

AC XY:

29354

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.396

Gnomad4 AMR

AF:

0.306

Gnomad4 ASJ

AF:

0.434

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.394

Alfa

AF:

0.418

Hom.:

25026

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

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;.;.

MutationTaster

Benign

1.0

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over