16-1781652-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001257370.2(EME2):c.*5414T>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 0.81 in 693,660 control chromosomes in the GnomAD database, including 229,467 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 0.84 (54683 hom., cov: 28)
  • Exomes 𝑓: 0.80 (174784 hom.)
• Consequence: EME2 NM_001257370.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

Genes affected

EME2 (HGNC:27289): (essential meiotic structure-specific endonuclease subunit 2) EME2 forms a heterodimer with MUS81 (MIM 606591) that functions as an XPF (MIM 278760)-type flap/fork endonuclease in DNA repair (Ciccia et al., 2007 [PubMed 17289582]).[supplied by OMIM, Mar 2008]

SPSB3 (HGNC:30629): (splA/ryanodine receptor domain and SOCS box containing 3) Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EME2	NM_001257370.2	c.*5414T>C		3_prime_UTR_variant	8/8	ENST00000568449.7
SPSB3	NM_080861.4	c.-12-157A>G		intron_variant		ENST00000566339.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EME2	ENST00000568449.7	c.*5414T>C		3_prime_UTR_variant	8/8	1	NM_001257370.2	P1
SPSB3	ENST00000566339.6	c.-12-157A>G		intron_variant		1	NM_080861.4	P1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128109 AN: 151672 Hom.: 54623 Cov.: 28

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.848

GnomAD4 exome AF: 0.801 AC: 433842 AN: 541870 Hom.: 174784 Cov.: 7 AF XY: 0.796 AC XY: 224489 AN XY: 281924

Gnomad4 AFR exome AF: 0.958

Gnomad4 AMR exome AF: 0.808

Gnomad4 ASJ exome AF: 0.861

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.817

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.845 AC: 128229 AN: 151790 Hom.: 54683 Cov.: 28 AF XY: 0.835 AC XY: 61924 AN XY: 74138

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.849

Alfa AF: 0.829 Hom.: 50317

Bravo AF: 0.863

Asia WGS AF: 0.738 AC: 2567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.0
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1178436; hg19: chr16-1831653; COSMIC: COSV51905158; COSMIC: COSV51905158;