dbSNP rs12450550: EME1:p.Ile350Thr (chr17-50378832-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152463.4(EME1):c.1049T>C(p.Ile350Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,614,056 control chromosomes in the GnomAD database, including 55,826 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3777 hom., cov: 32)

Exomes 𝑓: 0.26 ( 52049 hom. )

Consequence

EME1
NM_152463.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

EME1 (HGNC:24965): (essential meiotic structure-specific endonuclease 1) This gene encodes a protein that complexes with methyl methanesulfonate-sensitive UV-sensitive 81 protein to form an endonuclease complex. The encoded protein interacts with specifc DNA structures including nicked Holliday junctions, 3'-flap structures and aberrant replication fork structures. This protein may be involved in repairing DNA damage and in maintaining genomic stability. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

EME1 links:

LRRC59 (HGNC:28817): (leucine rich repeat containing 59) Enables RNA binding activity and cadherin binding activity. Predicted to be involved in positive regulation of Ras protein signal transduction and signal transduction. Located in endoplasmic reticulum and mitochondrial nucleoid. [provided by Alliance of Genome Resources, Apr 2022]

LRRC59 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004383743).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EME1	NM_152463.4 link	c.1049T>C	p.Ile350Thr	missense_variant	Exon 5 of 9	ENST00000338165.9	NP_689676.2	Q96AY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EME1	ENST00000338165.9 link	c.1049T>C	p.Ile350Thr	missense_variant	Exon 5 of 9	2	NM_152463.4	ENSP00000339897.4		Q96AY2-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30902

AN:

152060

Hom.:

3776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0835

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0862

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.191

GnomAD3 exomes

AF:

0.227

AC:

57084

AN:

251464

Hom.:

7538

AF XY:

0.223

AC XY:

30292

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0804

Gnomad AMR exome

AF:

0.290

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.0731

Gnomad SAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.272

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.259

AC:

378471

AN:

1461878

Hom.:

52049

Cov.:

AF XY:

0.255

AC XY:

185253

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0756

Gnomad4 AMR exome

AF:

0.285

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.0884

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.308

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.203

AC:

30905

AN:

152178

Hom.:

3777

Cov.:

AF XY:

0.201

AC XY:

14990

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0833

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.0866

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.247

Hom.:

12332

Bravo

AF:

0.194

TwinsUK

AF:

0.297

AC:

1103

ALSPAC

AF:

0.275

AC:

1061

ESP6500AA

AF:

0.0810

AC:

357

ESP6500EA

AF:

0.261

AC:

2244

ExAC

AF:

0.224

AC:

27188

Asia WGS

AF:

0.130

AC:

451

AN:

3478

EpiCase

AF:

0.254

EpiControl

AF:

0.253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.64

T;T;.

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.060

T;T;T

Sift4G

Benign

0.086

T;T;T

Polyphen

0.80

P;P;P

Vest4

0.069

MPC

0.080

ClinPred

0.011

GERP RS

2.1

Varity_R

0.082

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over