Genetic Variant NM_001257370.2:c.*5414T>C (chr16-1781652-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.149

Publications

14 publications found

Variant links:

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]

EME2 links:

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]

SPSB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EME2	NM_001257370.2 link	c.*5414T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000568449.7	NP_001244299.1	A4GXA9-1
SPSB3	NM_080861.4 link	c.-12-157A>G		intron_variant	Intron 1 of 6	ENST00000566339.6	NP_543137.2	Q6PJ21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EME2	ENST00000568449.7 link	c.*5414T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001257370.2	ENSP00000457353.1		A4GXA9-1
SPSB3	ENST00000566339.6 link	c.-12-157A>G		intron_variant	Intron 1 of 6	1	NM_080861.4	ENSP00000457206.1		Q6PJ21

Frequencies

GnomAD3 genomes

AF:

0.845

AC:

128109

AN:

151672

Hom.:

54623

Cov.:

show subpopulations

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.:

AF XY:

0.796

AC XY:

224489

AN XY:

281924

show subpopulations

African (AFR)

AF:

0.958

AC:

13327

AN:

13910

American (AMR)

AF:

0.808

AC:

15162

AN:

18756

Ashkenazi Jewish (ASJ)

AF:

0.861

AC:

12226

AN:

14194

East Asian (EAS)

AF:

0.701

AC:

22139

AN:

31564

South Asian (SAS)

AF:

0.726

AC:

34317

AN:

47266

European-Finnish (FIN)

AF:

0.725

AC:

26583

AN:

36682

Middle Eastern (MID)

AF:

0.858

AC:

1851

AN:

2158

European-Non Finnish (NFE)

AF:

0.817

AC:

284699

AN:

348448

Other (OTH)

AF:

0.815

AC:

23538

AN:

28892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4443

8887

13330

17774

22217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2802

5604

8406

11208

14010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.845

AC:

128229

AN:

151790

Hom.:

54683

Cov.:

AF XY:

0.835

AC XY:

61924

AN XY:

74138

show subpopulations

African (AFR)

AF:

0.956

AC:

39609

AN:

41418

American (AMR)

AF:

0.823

AC:

12559

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.864

AC:

3000

AN:

3472

East Asian (EAS)

AF:

0.737

AC:

3790

AN:

5140

South Asian (SAS)

AF:

0.735

AC:

3508

AN:

4772

European-Finnish (FIN)

AF:

0.714

AC:

7496

AN:

10502

Middle Eastern (MID)

AF:

0.884

AC:

258

AN:

292

European-Non Finnish (NFE)

AF:

0.816

AC:

55421

AN:

67928

Other (OTH)

AF:

0.849

AC:

1782

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

980

1959

2939

3918

4898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.833

Hom.:

137424

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

(source)

DANN

Benign

0.64

PhyloP100

-0.15

PromoterAI

0.0094

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over