1-240801508-A-C

Variant names:

• chr1-240801508-A-C
• NM_001364886.1:c.1360T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 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. 16/22 in silico tools predict a benign outcome for this variant. 2/2 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
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07718098).

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.1360T>G	p.Ser454Ala	missense splice_region	Exon 17 of 19	NP_001351815.1	P49802-1
	RGS7	NM_002924.6		c.1360T>G	p.Ser454Ala	missense splice_region	Exon 17 of 18	NP_002915.3
	RGS7	NM_001374814.1		c.1201T>G	p.Ser401Ala	missense splice_region	Exon 15 of 17	NP_001361743.1	A0A8I5QJU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.1360T>G	p.Ser454Ala	missense splice_region	Exon 17 of 19	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.1360T>G	p.Ser454Ala	missense splice_region	Exon 17 of 18	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.1359+1396T>G		intron	N/A	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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	0.064
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
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N
PhyloP100		6.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.075
Sift	Benign	0.92	T
Sift4G	Benign	0.72	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
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

hg19: chr1-240964808;