NM_001257370.2:c.*5414T>A

Variant names:

• chr16-1781652-T-A
• rs1178436
• NM_001257370.2:c.*5414T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B.

Score: -2 - Likely Benign

-2

PM2BP4_Strong

The NM_001257370.2(EME2):​c.*5414T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EME2 NM_001257370.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 14 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EME2	NM_001257370.2	c.*5414T>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000568449.7	NP_001244299.1
SPSB3	NM_080861.4	c.-12-157A>T		intron_variant	Intron 1 of 6	ENST00000566339.6	NP_543137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EME2	ENST00000568449.7	c.*5414T>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_001257370.2	ENSP00000457353.1
SPSB3	ENST00000566339.6	c.-12-157A>T		intron_variant	Intron 1 of 6	1	NM_080861.4	ENSP00000457206.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 542288 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 282122

African (AFR) AF: 0.00 AC: 0 AN: 13918

American (AMR) AF: 0.00 AC: 0 AN: 18758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14200

East Asian (EAS) AF: 0.00 AC: 0 AN: 31586

South Asian (SAS) AF: 0.00 AC: 0 AN: 47280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2158

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 348740

Other (OTH) AF: 0.00 AC: 0 AN: 28912

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.78
PhyloP100		-0.15
PromoterAI		0.015	Neutral

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: rs1178436; hg19: chr16-1831653;