3-158732292-C-G

Position:

• chr3-158732292-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000237696.10(RARRES1):​c.124G>C​(p.Asp42His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D42A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RARRES1 ENST00000237696.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.50

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04717323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARRES1	NM_206963.2	c.124G>C	p.Asp42His	missense_variant	1/6	ENST00000237696.10	NP_996846.1
RARRES1	NM_002888.4	c.124G>C	p.Asp42His	missense_variant	1/4		NP_002879.2
RARRES1	XM_005247686.6	c.124G>C	p.Asp42His	missense_variant	1/6		XP_005247743.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARRES1	ENST00000237696.10	c.124G>C	p.Asp42His	missense_variant	1/6	1	NM_206963.2	ENSP00000237696	P1
	ENST00000465477.5			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.124G>C (p.D42H) alteration is located in exon 1 (coding exon 1) of the RARRES1 gene. This alteration results from a G to C substitution at nucleotide position 124, causing the aspartic acid (D) at amino acid position 42 to be replaced by a histidine (H). 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	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.47
DANN	Benign	0.49
DEOGEN2	Benign	0.00030	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.30	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.047	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.60	N;N
REVEL	Benign	0.0080
Sift	Benign	0.31	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.0020	B;B
Vest4		0.059
MutPred		0.075		Loss of stability (P = 0.1717);Loss of stability (P = 0.1717);
MVP		0.067
MPC		0.52
ClinPred		0.079	T
GERP RS		-0.68
Varity_R		0.046
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-158450081;