Variant 20-31477902-G-A 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_014012.6(REM1):c.415G>A(p.Glu139Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,608,154 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 0.000085 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

REM1
NM_014012.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

Variant links:

Genes affected

REM1 (HGNC:15922): (RRAD and GEM like GTPase 1) The protein encoded by this gene is a GTPase and member of the RAS-like GTP-binding protein family. The encoded protein is expressed in endothelial cells, where it promotes reorganization of the actin cytoskeleton and morphological changes in the cells. [provided by RefSeq, Jul 2008]

REM1 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=0.191657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REM1	NM_014012.6 linkuse as main transcript	c.415G>A	p.Glu139Lys	missense_variant	3/5	ENST00000201979.3	NP_054731.2	O75628
REM1	XM_005260404.1 linkuse as main transcript	c.439G>A	p.Glu147Lys	missense_variant	3/5		XP_005260461.1
REM1	XM_017027833.2 linkuse as main transcript	c.439G>A	p.Glu147Lys	missense_variant	3/5		XP_016883322.1
REM1	XM_011528795.1 linkuse as main transcript	c.433G>A	p.Glu145Lys	missense_variant	3/5		XP_011527097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REM1	ENST00000201979.3 linkuse as main transcript	c.415G>A	p.Glu139Lys	missense_variant	3/5	1	NM_014012.6	ENSP00000201979.2		O75628

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000807

AC:

AN:

247782

Hom.:

AF XY:

0.0000673

AC XY:

AN XY:

133822

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000405

AC:

AN:

1456026

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

724484

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.000337

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000307

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.0000500

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000988

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

Jul 02, 2024

The c.415G>A (p.E139K) alteration is located in exon 3 (coding exon 2) of the REM1 gene. This alteration results from a G to A substitution at nucleotide position 415, causing the glutamic acid (E) at amino acid position 139 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

M_CAP

Benign

0.053

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.55

Sift

Benign

0.15

Sift4G

Benign

0.092

Polyphen

0.34

Vest4

0.52

MVP

0.92

MPC

0.26

ClinPred

0.12

GERP RS

4.5

Varity_R

0.27

gMVP

0.51

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