chr16-269358-G-T

Variant names:

• chr16-269358-G-T
• rs1018129727
• NM_183337.3:c.1315C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_183337.3(RGS11):​c.1315C>A​(p.Arg439Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RGS11 NM_183337.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 0 publications found

Genes affected

RGS11 (HGNC:9993): (regulator of G protein signaling 11) The protein encoded by this gene belongs to the RGS (regulator of G protein signaling) family. Members of the RGS family act as GTPase-activating proteins on the alpha subunits of heterotrimeric, signal-transducing G proteins. This protein inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Alternative splicing occurs at this locus and four transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2013]

FAM234A (HGNC:14163): (family with sequence similarity 234 member A) Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286901 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=2.15 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183337.3. 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
	RGS11	NM_183337.3	MANE Select	c.1315C>A	p.Arg439Arg	synonymous	Exon 17 of 17	NP_899180.1	O94810-1
	RGS11	NM_001286485.2		c.1282C>A	p.Arg428Arg	synonymous	Exon 16 of 16	NP_001273414.1	O94810-2
	RGS11	NM_003834.3		c.1252C>A	p.Arg418Arg	synonymous	Exon 17 of 17	NP_003825.1	O94810-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS11	ENST00000397770.8	TSL:1 MANE Select	c.1315C>A	p.Arg439Arg	synonymous	Exon 17 of 17	ENSP00000380876.3	O94810-1
	RGS11	ENST00000359740.6	TSL:1	c.1282C>A	p.Arg428Arg	synonymous	Exon 16 of 16	ENSP00000352778.5	O94810-2
	RGS11	ENST00000316163.9	TSL:1	c.1252C>A	p.Arg418Arg	synonymous	Exon 17 of 17	ENSP00000319069.5	O94810-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450868 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720732

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

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 43000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.00 AC: 0 AN: 39332

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107504

Other (OTH) AF: 0.00 AC: 0 AN: 59956

⚠️ 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.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1018129727; hg19: chr16-319357;