1-240776206-G-A

Variant names:

• chr1-240776206-G-A
• rs267598449
• ENST00000366565.5:c.1421C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002924.6(RGS7):​c.1421C>T​(p.Ser474Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S474C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS7 NM_002924.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.89
• 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

ENSG00000226919 (HGNC:):

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=0.15357852).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002924.6. 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.*14C>T		3_prime_UTR	Exon 19 of 19	NP_001351815.1	P49802-1
	RGS7	NM_002924.6		c.1421C>T	p.Ser474Phe	missense	Exon 18 of 18	NP_002915.3
	RGS7	NM_001282778.2		c.1367C>T	p.Ser456Phe	missense	Exon 17 of 17	NP_001269707.1	P49802-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000366565.5	TSL:1	c.1421C>T	p.Ser474Phe	missense	Exon 18 of 18	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.1367C>T	p.Ser456Phe	missense	Exon 17 of 17	ENSP00000355522.1	P49802-2
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.*14C>T		3_prime_UTR	Exon 19 of 19	ENSP00000404399.2	P49802-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.9
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.32		Loss of disorder (P = 0.0345)
MVP		0.14
MPC		0.81
ClinPred		0.84	D
GERP RS		5.3
gMVP		0.27
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs267598449; hg19: chr1-240939506; COSMIC: COSV58542189; COSMIC: COSV58542189;