3-158732163-C-T

Variant names:

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

Variant summary

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

The NM_206963.2(RARRES1):​c.253G>A​(p.Glu85Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000797 in 1,254,446 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E85Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: RARRES1 NM_206963.2 missense
• Clinical Significance: Not reported in ClinVar
• 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>A	p.Glu85Lys	missense	Exon 1 of 6	NP_996846.1	P49788-1
	RARRES1	NM_002888.4		c.253G>A	p.Glu85Lys	missense	Exon 1 of 4	NP_002879.2
	LOC100287290	NR_171780.1		n.-198C>T		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>A	p.Glu85Lys	missense	Exon 1 of 6	ENSP00000237696.5	P49788-1
	RARRES1	ENST00000479756.1	TSL:1	c.253G>A	p.Glu85Lys	missense	Exon 1 of 4	ENSP00000418556.1	P49788-2
	RARRES1	ENST00000879325.1		c.253G>A	p.Glu85Lys	missense	Exon 1 of 6	ENSP00000549384.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.97e-7 AC: 1 AN: 1254446 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 615312

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

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

Ashkenazi Jewish (ASJ) AF: 0.0000508 AC: 1 AN: 19688

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 59718

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: 0.00 AC: 0 AN: 1019948

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.72
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.012
Sift	Benign	0.83	T
Sift4G	Benign	0.52	T
Polyphen		0.088	B
Vest4		0.091
MutPred		0.48		Gain of MoRF binding (P = 9e-04)
MVP		0.061
MPC		0.52
ClinPred		0.066	T
GERP RS		-5.8
PromoterAI		-0.19	Neutral
Varity_R		0.045
gMVP		0.17
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		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;