1-241098753-C-T

Variant names:

• chr1-241098753-C-T
• rs758148829
• NM_001364886.1:c.88G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001364886.1(RGS7):​c.88G>A​(p.Val30Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,607,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: RGS7 NM_001364886.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.426
• Publications: 3 publications found

Genes affected

RGS7 (HGNC:10003): (regulator of G protein signaling 7) Enables G-protein beta-subunit binding activity and GTPase activator activity. Involved in positive regulation of GTPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RGS7 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

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=0.05962655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364886.1. 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
	RGS7	NM_001364886.1	MANE Select	c.88G>A	p.Val30Ile	missense	Exon 3 of 19	NP_001351815.1	P49802-1
	RGS7	NM_002924.6		c.88G>A	p.Val30Ile	missense	Exon 3 of 18	NP_002915.3
	RGS7	NM_001282775.2		c.88G>A	p.Val30Ile	missense	Exon 3 of 18	NP_001269704.1	P49802-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.88G>A	p.Val30Ile	missense	Exon 3 of 19	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.88G>A	p.Val30Ile	missense	Exon 3 of 18	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.88G>A	p.Val30Ile	missense	Exon 3 of 17	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250572 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000131 AC: 19 AN: 1455880 Hom.: 0 Cov.: 28 AF XY: 0.0000124 AC XY: 9 AN XY: 724750

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.0000447 AC: 2 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86158

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1107360

Other (OTH) AF: 0.00 AC: 0 AN: 60226

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152088 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10590

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Benign	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.85
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.32	N
PhyloP100		0.43
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.10	B
Vest4		0.31
MVP		0.17
MPC		0.63
ClinPred		0.090	T
GERP RS		5.2
gMVP		0.68
Mutation Taster		=264/36	polymorphism

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

Other links and lift over

dbSNP: rs758148829; hg19: chr1-241262053; COSMIC: COSV58536063;