NM_020834.3:c.1261G>C

Variant names:

• chr14-23275967-C-G
• rs746834504
• NM_020834.3:c.1261G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_020834.3(HOMEZ):​c.1261G>C​(p.Asp421His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: HOMEZ NM_020834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38836038).

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.1261G>C	p.Asp421His	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.1261G>C	p.Asp421His	missense	Exon 2 of 2	ENSP00000350049.4	Q8IX15-1
	HOMEZ	ENST00000561013.3	TSL:2	c.1267G>C	p.Asp423His	missense	Exon 3 of 3	ENSP00000453979.1	Q8IX15-3
	HOMEZ	ENST00000673724.1		c.928G>C	p.Asp310His	missense	Exon 3 of 3	ENSP00000501153.1	A0A669KB72

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 246154 AF XY: 0.00000749

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000224

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460574 Hom.: 0 Cov.: 36 AF XY: 0.00000688 AC XY: 5 AN XY: 726498

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111320

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000826 AC: 1

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	Pathogenic	0.78
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.47		Loss of catalytic residue at D421 (P = 0.0022)
MVP		0.38
MPC		0.96
ClinPred		0.76	D
GERP RS		5.8
Varity_R		0.46
gMVP		0.72
Mutation Taster		=57/43	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

dbSNP: rs746834504; hg19: chr14-23745176;