14-23275803-C-G

Position:

• chr14-23275803-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000357460.7(HOMEZ):​c.1425G>C​(p.Gln475His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOMEZ ENST00000357460.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.370

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26670566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOMEZ	NM_020834.3	c.1425G>C	p.Gln475His	missense_variant	2/2	ENST00000357460.7	NP_065885.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOMEZ	ENST00000357460.7	c.1425G>C	p.Gln475His	missense_variant	2/2	1	NM_020834.3	ENSP00000350049	P2
HOMEZ	ENST00000561013.3	c.1431G>C	p.Gln477His	missense_variant	3/3	2		ENSP00000453979	A2
HOMEZ	ENST00000673724.1	c.1092G>C	p.Gln364His	missense_variant	3/3			ENSP00000501153	A2
HOMEZ	ENST00000606731.2	c.915G>C	p.Gln305His	missense_variant	2/2	2		ENSP00000475307

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1425G>C (p.Q475H) 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 1425, causing the glutamine (Q) at amino acid position 475 to be replaced by a histidine (H). 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	0.18
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	0.90	L;.;.
MutationTaster	Benign	0.60	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N;N;.
REVEL	Benign	0.28
Sift	Benign	0.12	T;T;.
Sift4G	Benign	0.074	T;T;D
Polyphen		1.0	D;.;.
Vest4		0.26
MutPred		0.26		Loss of helix (P = 0.1299);.;.;
MVP		0.93
MPC		0.78
ClinPred		0.48	T
GERP RS		6.2
Varity_R		0.27
gMVP		0.31

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: chr14-23745012;