Variant 14-23276221-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020834.3(HOMEZ):c.1007G>T(p.Arg336Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000539 in 1,613,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 0 hom. )

Consequence

HOMEZ
NM_020834.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.694

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009427726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMEZ	NM_020834.3 linkuse as main transcript	c.1007G>T	p.Arg336Leu	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.1007G>T	p.Arg336Leu	missense_variant	2/2	1	NM_020834.3	P2	Q8IX15-1
HOMEZ	ENST00000561013.3 linkuse as main transcript	c.1013G>T	p.Arg338Leu	missense_variant	3/3	2		A2	Q8IX15-3
HOMEZ	ENST00000673724.1 linkuse as main transcript	c.674G>T	p.Arg225Leu	missense_variant	3/3			A2
HOMEZ	ENST00000606731.2 linkuse as main transcript	c.497G>T	p.Arg166Leu	missense_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000631

AC:

157

AN:

248984

Hom.:

AF XY:

0.000681

AC XY:

AN XY:

135044

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00121

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000561

AC:

820

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000556

AC XY:

404

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.000651

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000329

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.000306

ExAC

AF:

0.000951

AC:

115

EpiCase

AF:

0.000273

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.1007G>T (p.R336L) alteration is located in exon 2 (coding exon 2) of the HOMEZ gene. This alteration results from a G to T substitution at nucleotide position 1007, causing the arginine (R) at amino acid position 336 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.0012

T;.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.86

D;D;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.0094

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.79

N;N;.

REVEL

Benign

0.034

Sift

Benign

0.21

T;T;.

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.19

MVP

0.11

MPC

0.30

ClinPred

0.021

GERP RS

0.77

Varity_R

0.095

gMVP

0.52

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over