1-240801508-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001364886.1(RGS7):c.1360T>G(p.Ser454Ala) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS7 NM_001364886.1 missense, splice_region
• Scores: Splicing: ADA: 0.001338
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, RGS7
• BP4: Computational evidence support a benign effect (MetaRNN=0.07718098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS7	NM_001364886.1	c.1360T>G	p.Ser454Ala	missense_variant, splice_region_variant	17/19	ENST00000440928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS7	ENST00000440928.6	c.1360T>G	p.Ser454Ala	missense_variant, splice_region_variant	17/19	1	NM_001364886.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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

Jun 01, 2023

The c.1360T>G (p.S454A) alteration is located in exon 17 (coding exon 16) of the RGS7 gene. This alteration results from a T to G substitution at nucleotide position 1360, causing the serine (S) at amino acid position 454 to be replaced by an alanine (A). 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

-0.20

T

BayesDel_noAF

Benign

-0.52

Cadd

Benign

21

Dann

Benign

0.77

DEOGEN2

Benign

0.099

T;.

Eigen

Benign

-0.094

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.97

D

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.017

T

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.1

T

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;N;N

PrimateAI

Benign

0.38

T

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.075

Sift

Benign

0.92

T;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0080

.;B

Vest4

0.15

MutPred

0.16

.;Loss of phosphorylation at S454 (P = 0.037);

MVP

0.41

MPC

0.59

ClinPred

0.28

T

GERP RS

5.8

gMVP

0.070

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

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: chr1-240964808;