rs1057119

Positions:

• chr14-23277060-C-G
• chr14-23277060-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020834.3(HOMEZ):​c.168G>C​(p.Thr56Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,613,728 control chromosomes in the GnomAD database, including 40,760 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3185 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37575 hom.)
• Consequence: HOMEZ NM_020834.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOMEZ	NM_020834.3	c.168G>C	p.Thr56Thr	synonymous_variant	2/2	ENST00000357460.7	NP_065885.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOMEZ	ENST00000357460.7	c.168G>C	p.Thr56Thr	synonymous_variant	2/2	1	NM_020834.3	ENSP00000350049.4
HOMEZ	ENST00000561013.3	c.174G>C	p.Thr58Thr	synonymous_variant	3/3	2		ENSP00000453979.1
HOMEZ	ENST00000673724.1	c.168G>C	p.Thr56Thr	synonymous_variant	2/3			ENSP00000501153.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29817 AN: 152002 Hom.: 3181 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.216

GnomAD3 exomes AF: 0.206 AC: 51165 AN: 248954 Hom.: 5486 AF XY: 0.207 AC XY: 27923 AN XY: 135176

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.154

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.223 AC: 326552 AN: 1461608 Hom.: 37575 Cov.: 38 AF XY: 0.222 AC XY: 161622 AN XY: 727096

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.196 AC: 29837 AN: 152120 Hom.: 3185 Cov.: 32 AF XY: 0.197 AC XY: 14626 AN XY: 74354

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.220

Alfa AF: 0.129 Hom.: 326

Bravo AF: 0.189

Asia WGS AF: 0.191 AC: 661 AN: 3478

EpiCase AF: 0.226

EpiControl AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.0
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057119; hg19: chr14-23746269; COSMIC: COSV62536617; COSMIC: COSV62536617;