chr3-151880711-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033050.6(SUCNR1):​c.168C>A​(p.Asn56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000014 ( 0 hom. )

Consequence

SUCNR1
NM_033050.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.559
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]
AADACL2-AS1 (HGNC:50301): (AADACL2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.037169546).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUCNR1NM_033050.6 linkc.168C>A p.Asn56Lys missense_variant Exon 3 of 3 ENST00000362032.6 NP_149039.2 Q9BXA5
AADACL2-AS1NR_110202.1 linkn.319+47146G>T intron_variant Intron 1 of 3
AADACL2-AS1NR_110203.1 linkn.319+47146G>T intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SUCNR1ENST00000362032.6 linkc.168C>A p.Asn56Lys missense_variant Exon 3 of 3 1 NM_033050.6 ENSP00000355156.4 Q9BXA5
AADACL2-AS1ENST00000475855.1 linkn.319+47146G>T intron_variant Intron 1 of 3 5
AADACL2-AS1ENST00000483843.6 linkn.439+36904G>T intron_variant Intron 2 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461800
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727214
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 25, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.168C>A (p.N56K) alteration is located in exon 3 (coding exon 2) of the SUCNR1 gene. This alteration results from a C to A substitution at nucleotide position 168, causing the asparagine (N) at amino acid position 56 to be replaced by a lysine (K). 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
0.27
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.022
DANN
Benign
0.85
DEOGEN2
Benign
0.071
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.037
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.51
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.96
N
REVEL
Benign
0.042
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0030
B
Vest4
0.066
MutPred
0.62
Gain of methylation at N56 (P = 0.0257);
MVP
0.15
MPC
0.070
ClinPred
0.046
T
GERP RS
-5.4
Varity_R
0.067
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr3-151598499; API