3-158732193-C-A

Position:

chr3-158732193-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000237696.10(RARRES1):c.223G>T(p.Gly75Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000633 in 1,422,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

RARRES1
ENST00000237696.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.221

Variant links:

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]

RARRES1 links:

RARRES1 (HGNC:):

RARRES1 links:

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]

MFSD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARRES1	NM_206963.2 linkuse as main transcript	c.223G>T	p.Gly75Cys	missense_variant	1/6	ENST00000237696.10	NP_996846.1	P49788-1
RARRES1	NM_002888.4 linkuse as main transcript	c.223G>T	p.Gly75Cys	missense_variant	1/4		NP_002879.2	P49788-2
RARRES1	XM_005247686.6 linkuse as main transcript	c.223G>T	p.Gly75Cys	missense_variant	1/6		XP_005247743.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RARRES1	ENST00000237696.10 linkuse as main transcript	c.223G>T	p.Gly75Cys	missense_variant	1/6	1	NM_206963.2	ENSP00000237696.5	P49788-1
RARRES1	ENST00000479756.1 linkuse as main transcript	c.223G>T	p.Gly75Cys	missense_variant	1/4	1		ENSP00000418556.1	P49788-2
RARRES1	ENST00000498640.1 linkuse as main transcript	n.297G>T		non_coding_transcript_exon_variant	1/3	3
MFSD1	ENST00000486568.5 linkuse as main transcript	c.-221C>A		upstream_gene_variant		4		ENSP00000417414.1	C9JBA3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000472

AC:

AN:

1270396

Hom.:

Cov.:

AF XY:

0.00000641

AC XY:

AN XY:

624212

show subpopulations

Gnomad4 AFR exome

AF:

0.000237

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Jul 26, 2022

The c.223G>T (p.G75C) alteration is located in exon 1 (coding exon 1) of the RARRES1 gene. This alteration results from a G to T substitution at nucleotide position 223, causing the glycine (G) at amino acid position 75 to be replaced by a cysteine (C). 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

Pathogenic

0.57

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

T;.

Eigen

Benign

-0.021

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.48

T;T

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.9

M;M

MutationTaster

Benign

0.50

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-4.1

D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;D

Vest4

0.42

MutPred

0.78

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);

MVP

0.58

MPC

1.4

ClinPred

0.99

GERP RS

2.0

Varity_R

0.54

gMVP

0.50

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