Variant 14-23276162-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020834.3(HOMEZ):c.1066C>T(p.Arg356Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000174 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

HOMEZ
NM_020834.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1056245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMEZ	NM_020834.3 linkuse as main transcript	c.1066C>T	p.Arg356Cys	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.1066C>T	p.Arg356Cys	missense_variant	2/2	1	NM_020834.3	P2	Q8IX15-1
HOMEZ	ENST00000561013.3 linkuse as main transcript	c.1072C>T	p.Arg358Cys	missense_variant	3/3	2		A2	Q8IX15-3
HOMEZ	ENST00000673724.1 linkuse as main transcript	c.733C>T	p.Arg245Cys	missense_variant	3/3			A2
HOMEZ	ENST00000606731.2 linkuse as main transcript	c.556C>T	p.Arg186Cys	missense_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000149

AC:

AN:

248990

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

243

AN:

1461600

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

127

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000186

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000243

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000286

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000254

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000174

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

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

Dec 19, 2022

The c.1066C>T (p.R356C) alteration is located in exon 2 (coding exon 2) of the HOMEZ gene. This alteration results from a C to T substitution at nucleotide position 1066, causing the arginine (R) at amino acid position 356 to be replaced by a cysteine (C). 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

-0.29

BayesDel_noAF

Benign

-0.34

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.0047

T;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

0.98

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

N;N;.

REVEL

Benign

0.12

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.012

D;D;T

Polyphen

0.99

D;.;.

Vest4

0.26

MVP

0.42

MPC

0.91

ClinPred

0.14

GERP RS

5.9

Varity_R

0.19

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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