Variant chr1-240816364-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001364886.1(RGS7):c.736C>A(p.Pro246Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RGS7
NM_001364886.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.32

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2595177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS7	NM_001364886.1 linkuse as main transcript	c.736C>A	p.Pro246Thr	missense_variant	11/19	ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6 linkuse as main transcript	c.736C>A	p.Pro246Thr	missense_variant	11/19	1	NM_001364886.1	ENSP00000404399		P49802-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

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

AF:

0.0000263

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000793

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.736C>A (p.P246T) alteration is located in exon 11 (coding exon 10) of the RGS7 gene. This alteration results from a C to A substitution at nucleotide position 736, causing the proline (P) at amino acid position 246 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

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.;.;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.0081

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;.;L;L;L

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.11

T;T;T;T;T

Sift4G

Benign

0.071

T;T;T;T;T

Polyphen

0.72, 0.030

.;P;B;P;P

Vest4

0.58, 0.50, 0.64, 0.51

MutPred

0.17

.;.;Gain of phosphorylation at P246 (P = 0.0152);Gain of phosphorylation at P246 (P = 0.0152);Gain of phosphorylation at P246 (P = 0.0152);

MVP

0.093

MPC

1.2

ClinPred

0.76

GERP RS

6.1

gMVP

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over