1-182602099-G-C

Position:

• chr1-182602099-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002928.4(RGS16):​c.254C>G​(p.Thr85Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS16 NM_002928.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.66

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS16	NM_002928.4	c.254C>G	p.Thr85Arg	missense_variant	4/5	ENST00000367558.6	NP_002919.3
RGS16	XM_024448796.1	c.251C>G	p.Thr84Arg	missense_variant	4/5		XP_024304564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS16	ENST00000367558.6	c.254C>G	p.Thr85Arg	missense_variant	4/5	1	NM_002928.4	ENSP00000356529	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.254C>G (p.T85R) alteration is located in exon 4 (coding exon 4) of the RGS16 gene. This alteration results from a C to G substitution at nucleotide position 254, causing the threonine (T) at amino acid position 85 to be replaced by an arginine (R). 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	0.19
BayesDel_addAF	Benign	0.0094	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.52		Gain of solvent accessibility (P = 0.0503);
MVP		0.65
MPC		0.71
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.93
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr1-182571234;