chr20-31476495-C-T

Variant names:

• chr20-31476495-C-T
• rs375889740
• NM_014012.6:c.50C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014012.6(REM1):​c.50C>T​(p.Ala17Val) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,612,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: REM1 NM_014012.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 2 publications found

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]

DEFB124 (HGNC:18104): (defensin beta 124) Defensins are cysteine-rich cationic polypeptides that are important in the host immunologic response to invading microorganisms. This antimicrobial protein is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 20q11.1. The encoded protein may serve to enhance innate immunity in the prostate. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014012.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REM1	NM_014012.6	MANE Select	c.50C>T	p.Ala17Val	missense	Exon 2 of 5	NP_054731.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REM1	ENST00000201979.3	TSL:1 MANE Select	c.50C>T	p.Ala17Val	missense	Exon 2 of 5	ENSP00000201979.2	O75628
	REM1	ENST00000954465.1		c.50C>T	p.Ala17Val	missense	Exon 2 of 5	ENSP00000624524.1
	REM1	ENST00000954469.1		c.50C>T	p.Ala17Val	missense	Exon 2 of 5	ENSP00000624528.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000116 AC: 29 AN: 249568 AF XY: 0.000104

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000465

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000114 AC: 167 AN: 1460444 Hom.: 0 Cov.: 31 AF XY: 0.000113 AC XY: 82 AN XY: 726488

African (AFR) AF: 0.0000897 AC: 3 AN: 33458

American (AMR) AF: 0.000449 AC: 20 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.000123 AC: 137 AN: 1111330

Other (OTH) AF: 0.000116 AC: 7 AN: 60338

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74446

African (AFR) AF: 0.0000963 AC: 4 AN: 41558

American (AMR) AF: 0.000523 AC: 8 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000824 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.022	D
Polyphen		0.94	P
Vest4		0.43
MVP		0.92
MPC		0.55
ClinPred		0.29	T
GERP RS		4.5
Varity_R		0.16
gMVP		0.41
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs375889740; hg19: chr20-30064298;