14-23275745-C-T

Variant names:

• chr14-23275745-C-T
• rs1886335808
• NM_020834.3:c.1483G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020834.3(HOMEZ):​c.1483G>A​(p.Val495Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 3.86

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMEZ	NM_020834.3	c.1483G>A	p.Val495Met	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.1483G>A	p.Val495Met	missense_variant	Exon 2 of 2	1	NM_020834.3	ENSP00000350049.4
HOMEZ	ENST00000561013.3	c.1489G>A	p.Val497Met	missense_variant	Exon 3 of 3	2		ENSP00000453979.1
HOMEZ	ENST00000673724.1	c.1150G>A	p.Val384Met	missense_variant	Exon 3 of 3			ENSP00000501153.1
HOMEZ	ENST00000606731.2	c.*1G>A		downstream_gene_variant		2		ENSP00000475307.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1483G>A (p.V495M) alteration is located in exon 2 (coding exon 2) of the HOMEZ gene. This alteration results from a G to A substitution at nucleotide position 1483, causing the valine (V) at amino acid position 495 to be replaced by a methionine (M). 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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Benign	0.97	L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.048	D;D
Polyphen		1.0	D;.
Vest4		0.53
MutPred		0.54		Gain of MoRF binding (P = 0.1455);.;
MVP		0.97
MPC		0.84
ClinPred		0.95	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.50

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

Other links and lift over

dbSNP: rs1886335808; hg19: chr14-23744954;