Variant chr20-31476780-T-C 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.335T>C(p.Leu112Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,453,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

REM1
NM_014012.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.142

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:

DEFB124 (HGNC:):

DEFB124 links:

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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=0.07450104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REM1	NM_014012.6 linkuse as main transcript	c.335T>C	p.Leu112Pro	missense_variant	2/5	ENST00000201979.3	NP_054731.2	O75628
REM1	XM_005260404.1 linkuse as main transcript	c.335T>C	p.Leu112Pro	missense_variant	2/5		XP_005260461.1
REM1	XM_017027833.2 linkuse as main transcript	c.335T>C	p.Leu112Pro	missense_variant	2/5		XP_016883322.1
REM1	XM_011528795.1 linkuse as main transcript	c.335T>C	p.Leu112Pro	missense_variant	2/5		XP_011527097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REM1	ENST00000201979.3 linkuse as main transcript	c.335T>C	p.Leu112Pro	missense_variant	2/5	1	NM_014012.6	ENSP00000201979.2		O75628
DEFB124	ENST00000481595.1 linkuse as main transcript	n.-23A>G		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

242456

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

130944

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:

0.000173

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1453978

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

722820

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:

0.000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

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

Nov 14, 2024

The c.335T>C (p.L112P) alteration is located in exon 2 (coding exon 1) of the REM1 gene. This alteration results from a T to C substitution at nucleotide position 335, causing the leucine (L) at amino acid position 112 to be replaced by a proline (P). 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

0.057

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.068

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.53

M_CAP

Benign

0.048

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.86

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.090

REVEL

Benign

0.16

Sift

Benign

0.21

Sift4G

Benign

0.26

Polyphen

0.0090

Vest4

0.14

MutPred

0.59

Loss of stability (P = 0.0139);

MVP

0.71

MPC

0.34

ClinPred

0.060

GERP RS

3.5

Varity_R

0.39

gMVP

0.49

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