3-151881225-G-C

Variant names:

• chr3-151881225-G-C
• NM_033050.6:c.682G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033050.6(SUCNR1):​c.682G>C​(p.Glu228Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUCNR1 NM_033050.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87
• Publications: 0 publications found

Genes affected

SUCNR1 (HGNC:4542): (succinate receptor 1) This gene encodes a G-protein-coupled receptor for succinate, an intermediate molecule of the citric acid cycle. It is involved in the promotion of hematopoietic progenitor cell development, and it has a potential role in renovascular hypertension which has known correlations to renal failure, diabetes and atherosclerosis. [provided by RefSeq, Oct 2009]

AADACL2-AS1 (HGNC:50301): (AADACL2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20526087).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033050.6. 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
	SUCNR1	NM_033050.6	MANE Select	c.682G>C	p.Glu228Gln	missense	Exon 3 of 3	NP_149039.2
	AADACL2-AS1	NR_110202.1		n.319+46632C>G		intron	N/A
	AADACL2-AS1	NR_110203.1		n.319+46632C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCNR1	ENST00000362032.6	TSL:1 MANE Select	c.682G>C	p.Glu228Gln	missense	Exon 3 of 3	ENSP00000355156.4	Q9BXA5
	SUCNR1	ENST00000875328.1		c.682G>C	p.Glu228Gln	missense	Exon 2 of 2	ENSP00000545387.1
	SUCNR1	ENST00000943239.1		c.682G>C	p.Glu228Gln	missense	Exon 3 of 3	ENSP00000613298.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

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	0.096
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.9
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.092
Sift	Benign	0.19	T
Sift4G	Benign	0.076	T
Polyphen		0.45	P
Vest4		0.080
MutPred		0.34		Gain of glycosylation at P226 (P = 0.1221)
MVP		0.74
MPC		0.35
ClinPred		0.59	D
GERP RS		3.6
Varity_R		0.095
gMVP		0.43
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

hg19: chr3-151599013;