chr3-158732163-C-G

Variant names:

• chr3-158732163-C-G
• rs1404974771
• NM_206963.2:c.253G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_206963.2(RARRES1):​c.253G>C​(p.Glu85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,406,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: RARRES1 NM_206963.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.718
• Publications: 0 publications found

Genes affected

RARRES1 (HGNC:9867): (retinoic acid receptor responder 1) This gene was identified as a retinoid acid (RA) receptor-responsive gene. It encodes a type 1 membrane protein. The expression of this gene is upregulated by tazarotene as well as by retinoic acid receptors. The expression of this gene is found to be downregulated in prostate cancer, which is caused by the methylation of its promoter and CpG island. Alternatively spliced transcript variant encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

MFSD1 (HGNC:25874): (major facilitator superfamily domain containing 1) Predicted to enable protein homodimerization activity. Predicted to be involved in protein localization to lysosome and protein stabilization. Predicted to be located in lysosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000240207 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206963.2. 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
	RARRES1	NM_206963.2	MANE Select	c.253G>C	p.Glu85Gln	missense	Exon 1 of 6	NP_996846.1	P49788-1
	RARRES1	NM_002888.4		c.253G>C	p.Glu85Gln	missense	Exon 1 of 4	NP_002879.2
	LOC100287290	NR_171780.1		n.-198C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARRES1	ENST00000237696.10	TSL:1 MANE Select	c.253G>C	p.Glu85Gln	missense	Exon 1 of 6	ENSP00000237696.5	P49788-1
	RARRES1	ENST00000479756.1	TSL:1	c.253G>C	p.Glu85Gln	missense	Exon 1 of 4	ENSP00000418556.1	P49788-2
	RARRES1	ENST00000879325.1		c.253G>C	p.Glu85Gln	missense	Exon 1 of 6	ENSP00000549384.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152096 Hom.: 0 Cov.: 33

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000143 AC: 18 AN: 1254448 Hom.: 0 Cov.: 29 AF XY: 0.0000130 AC XY: 8 AN XY: 615314

African (AFR) AF: 0.00 AC: 0 AN: 24854

American (AMR) AF: 0.00 AC: 0 AN: 16380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19688

East Asian (EAS) AF: 0.00 AC: 0 AN: 27726

South Asian (SAS) AF: 0.00 AC: 0 AN: 59720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3664

European-Non Finnish (NFE) AF: 0.0000176 AC: 18 AN: 1019948

Other (OTH) AF: 0.00 AC: 0 AN: 51736

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152096 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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	0.097
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.2
DANN	Benign	0.83
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.72
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.012
Sift	Benign	0.59	T
Sift4G	Benign	0.69	T
Polyphen		0.042	B
Vest4		0.038
MutPred		0.42		Gain of MoRF binding (P = 0.03)
MVP		0.092
MPC		0.45
ClinPred		0.038	T
GERP RS		-5.8
PromoterAI		-0.35	Neutral
Varity_R		0.070
gMVP		0.15
Mutation Taster		=98/2	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: -2

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

Other links and lift over

dbSNP: rs1404974771; hg19: chr3-158449952;