Variant 15-48178134-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016132.5(MYEF2):c.104C>A(p.Pro35His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000769 in 1,585,868 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 (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 1 hom. )

Consequence

MYEF2
NM_016132.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.984

Variant links:

Genes affected

MYEF2 (HGNC:17940): (myelin expression factor 2) Enables RNA binding activity. Involved in myotube differentiation and neuron differentiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MYEF2 links:

CTXN2 (HGNC:31109): (cortexin 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CTXN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19230518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYEF2	NM_016132.5 linkuse as main transcript	c.104C>A	p.Pro35His	missense_variant	1/17	ENST00000324324.12	NP_057216.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYEF2	ENST00000324324.12 linkuse as main transcript	c.104C>A	p.Pro35His	missense_variant	1/17	1	NM_016132.5	ENSP00000316950	P4

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000732

AC:

AN:

191254

Hom.:

AF XY:

0.0000759

AC XY:

AN XY:

105454

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:

0.0000377

Gnomad FIN exome

AF:

0.000111

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000408

GnomAD4 exome

AF:

0.0000767

AC:

110

AN:

1433638

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

711182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000241

Gnomad4 FIN exome

AF:

0.000198

Gnomad4 NFE exome

AF:

0.0000837

Gnomad4 OTH exome

AF:

0.0000507

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000253

AC:

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

Sep 20, 2023

The c.104C>A (p.P35H) alteration is located in exon 1 (coding exon 1) of the MYEF2 gene. This alteration results from a C to A substitution at nucleotide position 104, causing the proline (P) at amino acid position 35 to be replaced by a histidine (H). 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

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.77

T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.54

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.53

N;N;.

REVEL

Benign

0.047

Sift

Uncertain

0.0080

D;D;.

Sift4G

Benign

0.34

T;T;T

Vest4

0.22

MVP

0.18

MPC

0.46

ClinPred

0.15

GERP RS

3.2

gMVP

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over