chr1-182604241-C-T

Position:

• chr1-182604241-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002928.4(RGS16):​c.19G>A​(p.Ala7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGS16 NM_002928.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0880

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072010666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS16	NM_002928.4	c.19G>A	p.Ala7Thr	missense_variant	1/5	ENST00000367558.6	NP_002919.3
RGS16	XM_024448796.1	c.19G>A	p.Ala7Thr	missense_variant	1/5		XP_024304564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS16	ENST00000367558.6	c.19G>A	p.Ala7Thr	missense_variant	1/5	1	NM_002928.4	ENSP00000356529	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399288 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Mar 07, 2023

The c.19G>A (p.A7T) alteration is located in exon 1 (coding exon 1) of the RGS16 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the alanine (A) at amino acid position 7 to be replaced by a threonine (T). 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	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.94	L
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.037
Sift	Benign	0.18	T
Sift4G	Benign	0.25	T
Polyphen		0.0090	B
Vest4		0.057
MutPred		0.23		Gain of phosphorylation at A7 (P = 0.0564);
MVP		0.67
MPC		0.15
ClinPred		0.38	T
GERP RS		2.3
Varity_R		0.093
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs1214210750; hg19: chr1-182573376;