Variant 20-31477891-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014012.6(REM1):c.404C>G(p.Thr135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,611,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

REM1
NM_014012.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REM1	NM_014012.6 linkuse as main transcript	c.404C>G	p.Thr135Ser	missense_variant	3/5	ENST00000201979.3	NP_054731.2	O75628
REM1	XM_005260404.1 linkuse as main transcript	c.428C>G	p.Thr143Ser	missense_variant	3/5		XP_005260461.1
REM1	XM_017027833.2 linkuse as main transcript	c.428C>G	p.Thr143Ser	missense_variant	3/5		XP_016883322.1
REM1	XM_011528795.1 linkuse as main transcript	c.422C>G	p.Thr141Ser	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.404C>G	p.Thr135Ser	missense_variant	3/5	1	NM_014012.6	ENSP00000201979.2		O75628

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152016

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:

0.000324

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000201

AC:

AN:

249012

Hom.:

AF XY:

0.000208

AC XY:

AN XY:

134542

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000416

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000277

AC:

404

AN:

1459680

Hom.:

Cov.:

AF XY:

0.000299

AC XY:

217

AN XY:

726114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.000353

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000145

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74230

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:

0.000324

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

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 06, 2022

The c.404C>G (p.T135S) alteration is located in exon 3 (coding exon 2) of the REM1 gene. This alteration results from a C to G substitution at nucleotide position 404, causing the threonine (T) at amino acid position 135 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.30

Eigen

Benign

0.041

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.094

MetaRNN

Uncertain

0.44

MetaSVM

Uncertain

0.040

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.54

Sift

Benign

0.31

Sift4G

Benign

0.44

Polyphen

0.046

Vest4

0.61

MutPred

0.77

Gain of disorder (P = 0.0505);

MVP

0.89

MPC

0.25

ClinPred

0.035

GERP RS

3.5

Varity_R

0.32

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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