chr3-151880738-C-T

Variant names:

• chr3-151880738-C-T
• rs79888638
• NM_033050.6:c.195C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_033050.6(SUCNR1):​c.195C>T​(p.Leu65Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,614,080 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (31 hom.)
• Consequence: SUCNR1 NM_033050.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.367
• Publications: 3 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 3-151880738-C-T is Benign according to our data. Variant chr3-151880738-C-T is described in ClinVar as Benign. ClinVar VariationId is 713065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.367 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00165 (251/152284) while in subpopulation EAS AF = 0.0374 (194/5188). AF 95% confidence interval is 0.0331. There are 3 homozygotes in GnomAd4. There are 146 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.195C>T	p.Leu65Leu	synonymous	Exon 3 of 3	NP_149039.2
	AADACL2-AS1	NR_110202.1		n.319+47119G>A		intron	N/A
	AADACL2-AS1	NR_110203.1		n.319+47119G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCNR1	ENST00000362032.6	TSL:1 MANE Select	c.195C>T	p.Leu65Leu	synonymous	Exon 3 of 3	ENSP00000355156.4	Q9BXA5
	SUCNR1	ENST00000875328.1		c.195C>T	p.Leu65Leu	synonymous	Exon 2 of 2	ENSP00000545387.1
	SUCNR1	ENST00000943239.1		c.195C>T	p.Leu65Leu	synonymous	Exon 3 of 3	ENSP00000613298.1

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 253 AN: 152166 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00363 AC: 913 AN: 251284 AF XY: 0.00370

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0400

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00144 AC: 2103 AN: 1461796 Hom.: 31 Cov.: 33 AF XY: 0.00160 AC XY: 1162 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0354 AC: 1406 AN: 39696

South Asian (SAS) AF: 0.00432 AC: 373 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000168 AC: 187 AN: 1111932

Other (OTH) AF: 0.00215 AC: 130 AN: 60394

GnomAD4 genome AF: 0.00165 AC: 251 AN: 152284 Hom.: 3 Cov.: 32 AF XY: 0.00196 AC XY: 146 AN XY: 74466

African (AFR) AF: 0.0000963 AC: 4 AN: 41552

American (AMR) AF: 0.000196 AC: 3 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0374 AC: 194 AN: 5188

South Asian (SAS) AF: 0.00683 AC: 33 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68022

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000942 Hom.: 1

Bravo AF: 0.00182

Asia WGS AF: 0.0210 AC: 74 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	3.9
DANN	Benign	0.74
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs79888638; hg19: chr3-151598526; COSMIC: COSV62911979;