1-182602094-A-C

Variant names:

• chr1-182602094-A-C
• rs1209468051
• NM_002928.4:c.259T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002928.4(RGS16):​c.259T>G​(p.Phe87Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RGS16 NM_002928.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.01
• Publications: 0 publications found

Genes affected

RGS16 (HGNC:9997): (regulator of G protein signaling 16) The protein encoded by this gene belongs to the 'regulator of G protein signaling' family. It inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits. It also may play a role in regulating the kinetics of signaling in the phototransduction cascade. [provided by RefSeq, Jul 2008]

ACMG classification

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, 0.932

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002928.4. 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
	RGS16	NM_002928.4	MANE Select	c.259T>G	p.Phe87Val	missense	Exon 4 of 5	NP_002919.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS16	ENST00000367558.6	TSL:1 MANE Select	c.259T>G	p.Phe87Val	missense	Exon 4 of 5	ENSP00000356529.5	O15492
	RGS16	ENST00000898513.1		c.256T>G	p.Phe86Val	missense	Exon 4 of 5	ENSP00000568572.1
	RGS16	ENST00000921546.1		c.253T>G	p.Phe85Val	missense	Exon 4 of 5	ENSP00000591605.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		9.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.74	P
Vest4		0.83
MutPred		0.84		Gain of ubiquitination at K84 (P = 0.1103)
MVP		0.78
MPC		0.59
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.97
gMVP		0.49
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1209468051; hg19: chr1-182571229;