1-240813625-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001364886.1(RGS7):c.949G>C(p.Glu317Gln) 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: 33)
• Consequence: RGS7 NM_001364886.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, RGS7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS7	NM_001364886.1	c.949G>C	p.Glu317Gln	missense_variant	13/19	ENST00000440928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS7	ENST00000440928.6	c.949G>C	p.Glu317Gln	missense_variant	13/19	1	NM_001364886.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK:

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2022

The c.949G>C (p.E317Q) alteration is located in exon 13 (coding exon 12) of the RGS7 gene. This alteration results from a G to C substitution at nucleotide position 949, causing the glutamic acid (E) at amino acid position 317 to be replaced by a glutamine (Q). 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

BayesDel_addAF

Benign

-0.0093

T

BayesDel_noAF

Benign

-0.25

Cadd

Pathogenic

26

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;.;.;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.97

D

LIST_S2

Uncertain

0.94

D;D;D;D;D

M_CAP

Benign

0.021

T

MetaRNN

Uncertain

0.49

T;T;T;T;T

MetaSVM

Benign

-0.73

T

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.73

T

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.012

D;D;D;D;D

Sift4G

Benign

0.075

T;D;T;T;T

Polyphen

1.0, 0.99, 0.99, 0.99

.;D;D;D;D

Vest4

0.55, 0.54, 0.50, 0.55

MutPred

0.18

.;.;Loss of glycosylation at S319 (P = 0.102);Loss of glycosylation at S319 (P = 0.102);Loss of glycosylation at S319 (P = 0.102);

MVP

0.49

MPC

1.0

ClinPred

0.96

D

GERP RS

5.8

gMVP

0.72

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: chr1-240976925;