14-23275723-C-T

Variant names:

• chr14-23275723-C-T
• rs1055061
• NM_020834.3:c.1505G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020834.3(HOMEZ):​c.1505G>A​(p.Arg502Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 1,610,850 control chromosomes in the GnomAD database, including 4,686 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R502L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.094 (1080 hom., cov: 31)
  • Exomes 𝑓: 0.058 (3606 hom.)
• Consequence: HOMEZ NM_020834.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014183521).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

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.1505G>A	p.Arg502Gln	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.1505G>A	p.Arg502Gln	missense	Exon 2 of 2	ENSP00000350049.4	Q8IX15-1
	HOMEZ	ENST00000561013.3	TSL:2	c.1511G>A	p.Arg504Gln	missense	Exon 3 of 3	ENSP00000453979.1	Q8IX15-3
	HOMEZ	ENST00000673724.1		c.1172G>A	p.Arg391Gln	missense	Exon 3 of 3	ENSP00000501153.1	A0A669KB72

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14210 AN: 151870 Hom.: 1074 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0582

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0278

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0735

GnomAD2 exomes AF: 0.0697 AC: 17015 AN: 244114 AF XY: 0.0727

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.0311

Gnomad ASJ exome AF: 0.0351

Gnomad EAS exome AF: 0.0608

Gnomad FIN exome AF: 0.0294

Gnomad NFE exome AF: 0.0478

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0579 AC: 84537 AN: 1458860 Hom.: 3606 Cov.: 36 AF XY: 0.0607 AC XY: 44037 AN XY: 725440

African (AFR) AF: 0.206 AC: 6883 AN: 33446

American (AMR) AF: 0.0331 AC: 1457 AN: 43970

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 934 AN: 26058

East Asian (EAS) AF: 0.0448 AC: 1775 AN: 39642

South Asian (SAS) AF: 0.164 AC: 14070 AN: 85856

European-Finnish (FIN) AF: 0.0303 AC: 1617 AN: 53306

Middle Eastern (MID) AF: 0.0647 AC: 373 AN: 5766

European-Non Finnish (NFE) AF: 0.0480 AC: 53325 AN: 1110510

Other (OTH) AF: 0.0680 AC: 4103 AN: 60306

GnomAD4 genome AF: 0.0937 AC: 14240 AN: 151990 Hom.: 1080 Cov.: 31 AF XY: 0.0928 AC XY: 6893 AN XY: 74304

African (AFR) AF: 0.203 AC: 8408 AN: 41390

American (AMR) AF: 0.0512 AC: 781 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3470

East Asian (EAS) AF: 0.0582 AC: 301 AN: 5176

South Asian (SAS) AF: 0.178 AC: 858 AN: 4814

European-Finnish (FIN) AF: 0.0278 AC: 295 AN: 10596

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0486 AC: 3306 AN: 67966

Other (OTH) AF: 0.0726 AC: 153 AN: 2106

Alfa AF: 0.0599 Hom.: 1956

Bravo AF: 0.0963

TwinsUK AF: 0.0426 AC: 158

ALSPAC AF: 0.0498 AC: 192

ESP6500AA AF: 0.195 AC: 840

ESP6500EA AF: 0.0468 AC: 399

ExAC AF: 0.0735 AC: 8902

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.074
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.20
Sift	Benign	0.085	T
Sift4G	Benign	0.075	T
Polyphen		0.23	B
Vest4		0.087
MPC		0.30
ClinPred		0.013	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.17
Mutation Taster		=76/24	polymorphism (auto)

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: rs1055061; hg19: chr14-23744932; COSMIC: COSV62537649; COSMIC: COSV62537649;