chr16-271029-C-T

Variant names:

• chr16-271029-C-T
• rs746233784
• NM_183337.3:c.934G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_183337.3(RGS11):​c.934G>A​(p.Val312Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,610,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: RGS11 NM_183337.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47
• Publications: 3 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]

ENSG00000286901 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17437246).
• BP6: Variant 16-271029-C-T is Benign according to our data. Variant chr16-271029-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3153785.Status of the report is criteria_provided_single_submitter, 1 stars.

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.934G>A	p.Val312Met	missense	Exon 13 of 17	NP_899180.1	O94810-1
	RGS11	NM_001286485.2		c.901G>A	p.Val301Met	missense	Exon 12 of 16	NP_001273414.1	O94810-2
	RGS11	NM_003834.3		c.871G>A	p.Val291Met	missense	Exon 13 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.934G>A	p.Val312Met	missense	Exon 13 of 17	ENSP00000380876.3	O94810-1
	RGS11	ENST00000359740.6	TSL:1	c.901G>A	p.Val301Met	missense	Exon 12 of 16	ENSP00000352778.5	O94810-2
	RGS11	ENST00000316163.9	TSL:1	c.871G>A	p.Val291Met	missense	Exon 13 of 17	ENSP00000319069.5	O94810-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151974 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000413 AC: 10 AN: 242078 AF XY: 0.0000375

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000873

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00000931

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1458090 Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 20 AN XY: 724892

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.0000447 AC: 2 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000474 AC: 4 AN: 84382

European-Finnish (FIN) AF: 0.0000578 AC: 3 AN: 51918

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111814

Other (OTH) AF: 0.0000498 AC: 3 AN: 60234

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151974 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74200

African (AFR) AF: 0.0000241 AC: 1 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4724

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.085
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.13
DANN	Benign	0.79
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.022
Sift	Benign	0.18	T
Sift4G	Benign	0.22	T
Polyphen		0.0090	B
Vest4		0.33
MutPred		0.58		Gain of disorder (P = 0.0567)
MVP		0.23
MPC		0.11
ClinPred		0.042	T
GERP RS		-7.1
Varity_R		0.042
gMVP		0.20
Mutation Taster		=92/8	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: rs746233784; hg19: chr16-321028; COSMIC: COSV51453134; COSMIC: COSV51453134;