Variant chr14-23275723-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.1505G>A(p.Arg502Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 1,610,850 control chromosomes in the GnomAD database, including 4,686 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 0.094 ( 1080 hom., cov: 31)

Exomes 𝑓: 0.058 ( 3606 hom. )

Consequence

HOMEZ
NM_020834.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

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=0.0014183521).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 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.1505G>A	p.Arg502Gln	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.1505G>A	p.Arg502Gln	missense_variant	2/2	1	NM_020834.3	P2	Q8IX15-1
HOMEZ	ENST00000561013.3 linkuse as main transcript	c.1511G>A	p.Arg504Gln	missense_variant	3/3	2		A2	Q8IX15-3
HOMEZ	ENST00000673724.1 linkuse as main transcript	c.1172G>A	p.Arg391Gln	missense_variant	3/3			A2
HOMEZ	ENST00000606731.2 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

14210

AN:

151870

Hom.:

1074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0512

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.0582

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.0278

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0487

Gnomad OTH

AF:

0.0735

GnomAD3 exomes

AF:

0.0697

AC:

17015

AN:

244114

Hom.:

989

AF XY:

0.0727

AC XY:

9607

AN XY:

132208

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.0311

Gnomad ASJ exome

AF:

0.0351

Gnomad EAS exome

AF:

0.0608

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.0478

Gnomad OTH exome

AF:

0.0572

GnomAD4 exome

AF:

0.0579

AC:

84537

AN:

1458860

Hom.:

3606

Cov.:

AF XY:

0.0607

AC XY:

44037

AN XY:

725440

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.0331

Gnomad4 ASJ exome

AF:

0.0358

Gnomad4 EAS exome

AF:

0.0448

Gnomad4 SAS exome

AF:

0.164

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.0480

Gnomad4 OTH exome

AF:

0.0680

GnomAD4 genome

AF:

0.0937

AC:

14240

AN:

151990

Hom.:

1080

Cov.:

AF XY:

0.0928

AC XY:

6893

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.0512

Gnomad4 ASJ

AF:

0.0320

Gnomad4 EAS

AF:

0.0582

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.0278

Gnomad4 NFE

AF:

0.0486

Gnomad4 OTH

AF:

0.0726

Alfa

AF:

0.0544

Hom.:

813

Bravo

AF:

0.0963

TwinsUK

AF:

0.0426

AC:

158

ALSPAC

AF:

0.0498

AC:

192

ESP6500AA

AF:

0.195

AC:

840

ESP6500EA

AF:

0.0468

AC:

399

ExAC

AF:

0.0735

AC:

8902

Asia WGS

AF:

0.137

AC:

479

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0053

T;.

Eigen

Benign

-0.074

Eigen_PC

Benign

0.057

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

N;.

MutationTaster

Benign

0.013

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.20

Sift

Benign

0.085

T;T

Sift4G

Benign

0.075

T;T

Polyphen

0.23

B;.

Vest4

0.087

MPC

0.30

ClinPred

0.013

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.17

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