dbSNP rs769017257: SUCNR1:p.Leu76Ile (chr3-151880769-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_033050.6(SUCNR1):c.226C>A(p.Leu76Ile) 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 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L76F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SUCNR1
NM_033050.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.63

Publications

0 publications found

Variant links:

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]

SUCNR1 links:

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

AADACL2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.892

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SUCNR1	NM_033050.6	MANE Select	c.226C>A	p.Leu76Ile	missense	Exon 3 of 3	NP_149039.2
AADACL2-AS1	NR_110202.1		n.319+47088G>T		intron	N/A
AADACL2-AS1	NR_110203.1		n.319+47088G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUCNR1	ENST00000362032.6	TSL:1 MANE Select	c.226C>A	p.Leu76Ile	missense	Exon 3 of 3	ENSP00000355156.4	Q9BXA5
SUCNR1	ENST00000875328.1		c.226C>A	p.Leu76Ile	missense	Exon 2 of 2	ENSP00000545387.1
SUCNR1	ENST00000943239.1		c.226C>A	p.Leu76Ile	missense	Exon 3 of 3	ENSP00000613298.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727224

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111984

Other (OTH)

AF:

0.00

AC:

AN:

60386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-0.80

MutationAssessor

Pathogenic

3.3

PhyloP100

2.6

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.71

MutPred

0.86

Loss of helix (P = 0.2022)

MVP

0.48

MPC

0.40

ClinPred

0.99

GERP RS

5.3

Varity_R

0.56

gMVP

0.27

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over