14-23275682-C-G

Variant names:

• chr14-23275682-C-G
• NM_020834.3:c.1546G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020834.3(HOMEZ):​c.1546G>C​(p.Glu516Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOMEZ NM_020834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38

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]

ACMG classification

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=0.21967304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMEZ	NM_020834.3	c.1546G>C	p.Glu516Gln	missense_variant	Exon 2 of 2	ENST00000357460.7	NP_065885.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMEZ	ENST00000357460.7	c.1546G>C	p.Glu516Gln	missense_variant	Exon 2 of 2	1	NM_020834.3	ENSP00000350049.4
HOMEZ	ENST00000561013.3	c.1552G>C	p.Glu518Gln	missense_variant	Exon 3 of 3	2		ENSP00000453979.1
HOMEZ	ENST00000673724.1	c.1213G>C	p.Glu405Gln	missense_variant	Exon 3 of 3			ENSP00000501153.1
HOMEZ	ENST00000606731.2	c.*64G>C		downstream_gene_variant		2		ENSP00000475307.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1546G>C (p.E516Q) alteration is located in exon 2 (coding exon 2) of the HOMEZ gene. This alteration results from a G to C substitution at nucleotide position 1546, causing the glutamic acid (E) at amino acid position 516 to be replaced by a glutamine (Q). 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	0.31
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0098	T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.89	P;.
Vest4		0.36
MutPred		0.24		Gain of sheet (P = 0.1539);.;
MVP		0.76
MPC		0.24
ClinPred		0.48	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.18
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-23744891;