rs1055375

Positions:

• chr14-23273087-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020834.3(HOMEZ):​c.*2488T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 415,016 control chromosomes in the GnomAD database, including 663 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 0.041 (174 hom., cov: 32)
  • Exomes 𝑓: 0.053 (489 hom.)
• Consequence: HOMEZ NM_020834.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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]

RNF212B (HGNC:20438): (ring finger protein 212B) Predicted to enable SUMO transferase activity. Predicted to be involved in homologous chromosome pairing at meiosis and protein sumoylation. Predicted to be active in synaptonemal complex. [provided by Alliance of Genome Resources, Apr 2022]

RNF212B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOMEZ	NM_020834.3	c.*2488T>C		3_prime_UTR_variant	2/2	ENST00000357460.7	NP_065885.2
RNF212B	NM_001282322.3	c.*196A>G		3_prime_UTR_variant	15/15	ENST00000430154.7	NP_001269251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOMEZ	ENST00000357460	c.*2488T>C		3_prime_UTR_variant	2/2	1	NM_020834.3	ENSP00000350049.4
RNF212B	ENST00000430154.7	c.*196A>G		3_prime_UTR_variant	15/15	5	NM_001282322.3	ENSP00000397830.2

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6270 AN: 152168 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0521

GnomAD4 exome AF: 0.0533 AC: 13995 AN: 262730 Hom.: 489 Cov.: 2 AF XY: 0.0534 AC XY: 7239 AN XY: 135672

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.0440

Gnomad4 ASJ exome AF: 0.0797

Gnomad4 EAS exome AF: 0.0000478

Gnomad4 SAS exome AF: 0.0229

Gnomad4 FIN exome AF: 0.0229

Gnomad4 NFE exome AF: 0.0661

Gnomad4 OTH exome AF: 0.0538

GnomAD4 genome AF: 0.0412 AC: 6268 AN: 152286 Hom.: 174 Cov.: 32 AF XY: 0.0386 AC XY: 2875 AN XY: 74454

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0497 Hom.: 29

Bravo AF: 0.0420

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1055375; hg19: chr14-23742296;