14-23276324-C-T

Variant names:

• chr14-23276324-C-T
• rs10131813
• NM_020834.3:c.904G>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.904G>A​(p.Ala302Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,613,070 control chromosomes in the GnomAD database, including 133,528 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.

• Frequency:
  • Genomes: 𝑓 0.40 (12233 hom., cov: 31)
  • Exomes 𝑓: 0.41 (121295 hom.)
• Consequence: HOMEZ NM_020834.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 31 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=0.0027455986).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 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.904G>A	p.Ala302Thr	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.904G>A	p.Ala302Thr	missense	Exon 2 of 2	ENSP00000350049.4	Q8IX15-1
	HOMEZ	ENST00000561013.3	TSL:2	c.910G>A	p.Ala304Thr	missense	Exon 3 of 3	ENSP00000453979.1	Q8IX15-3
	HOMEZ	ENST00000673724.1		c.571G>A	p.Ala191Thr	missense	Exon 3 of 3	ENSP00000501153.1	A0A669KB72

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60478 AN: 151738 Hom.: 12228 Cov.: 31

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.395

GnomAD2 exomes AF: 0.382 AC: 94692 AN: 248176 AF XY: 0.388

Gnomad AFR exome AF: 0.399

Gnomad AMR exome AF: 0.252

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.317

Gnomad FIN exome AF: 0.409

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.405 AC: 592262 AN: 1461212 Hom.: 121295 Cov.: 60 AF XY: 0.405 AC XY: 294546 AN XY: 726860

African (AFR) AF: 0.396 AC: 13255 AN: 33480

American (AMR) AF: 0.258 AC: 11502 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 11381 AN: 26110

East Asian (EAS) AF: 0.352 AC: 13965 AN: 39696

South Asian (SAS) AF: 0.365 AC: 31443 AN: 86232

European-Finnish (FIN) AF: 0.415 AC: 22151 AN: 53380

Middle Eastern (MID) AF: 0.464 AC: 2676 AN: 5768

European-Non Finnish (NFE) AF: 0.415 AC: 461490 AN: 1111532

Other (OTH) AF: 0.404 AC: 24399 AN: 60358

GnomAD4 genome AF: 0.398 AC: 60500 AN: 151858 Hom.: 12233 Cov.: 31 AF XY: 0.396 AC XY: 29354 AN XY: 74186

African (AFR) AF: 0.396 AC: 16402 AN: 41392

American (AMR) AF: 0.306 AC: 4674 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1506 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1656 AN: 5154

South Asian (SAS) AF: 0.348 AC: 1675 AN: 4812

European-Finnish (FIN) AF: 0.418 AC: 4393 AN: 10522

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28870 AN: 67938

Other (OTH) AF: 0.394 AC: 829 AN: 2106

Alfa AF: 0.416 Hom.: 35722

Bravo AF: 0.390

TwinsUK AF: 0.424 AC: 1573

ALSPAC AF: 0.418 AC: 1612

ESP6500AA AF: 0.379 AC: 1556

ESP6500EA AF: 0.429 AC: 3585

ExAC AF: 0.388 AC: 46867

EpiCase AF: 0.427

EpiControl AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.53
DEOGEN2	Benign	0.00022	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.2	N
PhyloP100		-0.14
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.87	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.23
ClinPred		0.0031	T
GERP RS		-2.6
Varity_R		0.030
gMVP		0.19
Mutation Taster		=100/0	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: rs10131813; hg19: chr14-23745533; COSMIC: COSV62536637; COSMIC: COSV62536637;