Variant chr17-50379083-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152463.4(EME1):c.1113-24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,854 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 1 hom. )

Consequence

EME1
NM_152463.4 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.206

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (MetaRNN=0.031651556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EME1	NM_152463.4 linkuse as main transcript	c.1113-24C>G		intron_variant		ENST00000338165.9	NP_689676.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EME1	ENST00000338165.9 linkuse as main transcript	c.1113-24C>G		intron_variant		2	NM_152463.4	ENSP00000339897	P1	Q96AY2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251344

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.1128C>G (p.F376L) alteration is located in exon 6 (coding exon 5) of the EME1 gene. This alteration results from a C to G substitution at nucleotide position 1128, causing the phenylalanine (F) at amino acid position 376 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.81

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.22

T;.

M_CAP

Benign

0.0042

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.031

Sift

Benign

1.0

T;T

Sift4G

Benign

0.95

T;T

Polyphen

0.0

B;B

Vest4

0.083

MutPred

0.46

Gain of sheet (P = 0.0016);Gain of sheet (P = 0.0016);

MVP

0.10

MPC

0.063

ClinPred

0.018

GERP RS

3.3

BranchPoint Hunter

3.0

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over