14-23276080-C-T

Variant names:

• chr14-23276080-C-T
• rs371112513
• NM_020834.3:c.1148G>A

Variant summary

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

The NM_020834.3(HOMEZ):​c.1148G>A​(p.Arg383His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,614,016 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: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: HOMEZ NM_020834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.51
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31455046).

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.1148G>A	p.Arg383His	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.1148G>A	p.Arg383His	missense	Exon 2 of 2	ENSP00000350049.4	Q8IX15-1
	HOMEZ	ENST00000561013.3	TSL:2	c.1154G>A	p.Arg385His	missense	Exon 3 of 3	ENSP00000453979.1	Q8IX15-3
	HOMEZ	ENST00000673724.1		c.815G>A	p.Arg272His	missense	Exon 3 of 3	ENSP00000501153.1	A0A669KB72

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000923 AC: 23 AN: 249152 AF XY: 0.000111

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000974

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000664 AC: 97 AN: 1461692 Hom.: 0 Cov.: 36 AF XY: 0.0000715 AC XY: 52 AN XY: 727126

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000224 AC: 10 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000720 AC: 80 AN: 1111860

Other (OTH) AF: 0.0000663 AC: 4 AN: 60374

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74486

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000437 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	Uncertain	0.35
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0054	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	1.0	L
PhyloP100		2.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.55
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.046	D
Polyphen		1.0	D
Vest4		0.33
MVP		0.94
MPC		0.98
ClinPred		0.22	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.39
Mutation Taster		=42/58	disease causing

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: rs371112513; hg19: chr14-23745289;