3-158732298-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_206963.2(RARRES1):c.118T>G(p.Ser40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,343,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 8.4e-7 ( 0 hom. )

Consequence

RARRES1
NM_206963.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.260

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:

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a glycosylation_site O-linked (Xyl...) (chondroitin sulfate) serine (size 0) in uniprot entity TIG1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053441435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RARRES1	NM_206963.2 linkuse as main transcript	c.118T>G	p.Ser40Ala	missense_variant	1/6	ENST00000237696.10
RARRES1	NM_002888.4 linkuse as main transcript	c.118T>G	p.Ser40Ala	missense_variant	1/4
RARRES1	XM_005247686.6 linkuse as main transcript	c.118T>G	p.Ser40Ala	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARRES1	ENST00000237696.10 linkuse as main transcript	c.118T>G	p.Ser40Ala	missense_variant	1/6	1	NM_206963.2	P1	P49788-1
	ENST00000465477.5 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

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:

8.39e-7

AC:

AN:

1191740

Hom.:

Cov.:

AF XY:

0.00000173

AC XY:

AN XY:

578166

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151262

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73918

show subpopulations

Gnomad4 AFR

AF:

0.0000245

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

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 09, 2021

The c.118T>G (p.S40A) alteration is located in exon 1 (coding exon 1) of the RARRES1 gene. This alteration results from a T to G substitution at nucleotide position 118, causing the serine (S) at amino acid position 40 to be replaced by an alanine (A). 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

0.066

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

Cadd

Benign

3.9

Dann

Benign

0.46

DEOGEN2

Benign

0.0021

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.17

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.31

N;N

REVEL

Benign

0.0060

Sift

Benign

0.45

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0

B;B

Vest4

0.061

MutPred

0.20

Loss of glycosylation at S40 (P = 5e-04);Loss of glycosylation at S40 (P = 5e-04);

MVP

0.095

MPC

0.43

ClinPred

0.044

GERP RS

-5.6

Varity_R

0.061

gMVP

0.11

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