chr14-23275919-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116497874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020834.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOMEZ	NM_020834.3	MANE Select	c.1309A>G	p.Thr437Ala	missense	Exon 2 of 2	NP_065885.2	Q8IX15-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOMEZ	ENST00000357460.7	TSL:1 MANE Select	c.1309A>G	p.Thr437Ala	missense	Exon 2 of 2	ENSP00000350049.4	Q8IX15-1
	HOMEZ	ENST00000561013.3	TSL:2	c.1315A>G	p.Thr439Ala	missense	Exon 3 of 3	ENSP00000453979.1	Q8IX15-3
	HOMEZ	ENST00000673724.1		c.976A>G	p.Thr326Ala	missense	Exon 3 of 3	ENSP00000501153.1	A0A669KB72

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

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25472

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 84990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107900

Other (OTH) AF: 0.00 AC: 0 AN: 60048

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.038
Sift	Benign	0.20	T
Sift4G	Benign	0.66	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
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr14-23745128;