14-23275919-T-C

Variant names:

• chr14-23275919-T-C
• NM_020834.3:c.1309A>G

Variant summary

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

The NM_020834.3(HOMEZ):​c.1309A>G​(p.Thr437Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HOMEZ NM_020834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51

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=0.116497874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMEZ	NM_020834.3	c.1309A>G	p.Thr437Ala	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.1309A>G	p.Thr437Ala	missense_variant	Exon 2 of 2	1	NM_020834.3	ENSP00000350049.4
HOMEZ	ENST00000561013.3	c.1315A>G	p.Thr439Ala	missense_variant	Exon 3 of 3	2		ENSP00000453979.1
HOMEZ	ENST00000673724.1	c.976A>G	p.Thr326Ala	missense_variant	Exon 3 of 3			ENSP00000501153.1
HOMEZ	ENST00000606731.2	c.799A>G	p.Thr267Ala	missense_variant	Exon 2 of 2	2		ENSP00000475307.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454422 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 722816

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1309A>G (p.T437A) alteration is located in exon 2 (coding exon 2) of the HOMEZ gene. This alteration results from a A to G substitution at nucleotide position 1309, causing the threonine (T) at amino acid position 437 to be replaced by an alanine (A). 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	0.075
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.58
DEOGEN2	Benign	0.0013	T;.;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.75	N;N;.
REVEL	Benign	0.038
Sift	Benign	0.20	T;T;.
Sift4G	Benign	0.66	T;T;T
Polyphen		0.28	B;.;.
Vest4		0.17
MutPred		0.26		Loss of glycosylation at T437 (P = 0);.;.;
MVP		0.41
MPC		0.47
ClinPred		0.13	T
GERP RS		3.4
Varity_R		0.032
gMVP		0.46

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: chr14-23745128;