NM_001364886.1:c.1375G>A

Variant names:

• chr1-240801493-C-T
• rs141557672
• NM_001364886.1:c.1375G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001364886.1(RGS7):​c.1375G>A​(p.Asp459Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000569 in 1,608,356 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. D459H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (0 hom.)
• Consequence: RGS7 NM_001364886.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.79
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.077212244).

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.1375G>A	p.Asp459Asn	missense	Exon 17 of 19	NP_001351815.1	P49802-1
	RGS7	NM_002924.6		c.1375G>A	p.Asp459Asn	missense	Exon 17 of 18	NP_002915.3
	RGS7	NM_001374814.1		c.1216G>A	p.Asp406Asn	missense	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.1375G>A	p.Asp459Asn	missense	Exon 17 of 19	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.1375G>A	p.Asp459Asn	missense	Exon 17 of 18	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.1359+1411G>A		intron	N/A	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes AF: 0.000336 AC: 51 AN: 151890 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000677

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000276 AC: 69 AN: 250172 AF XY: 0.000303

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000504

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000593 AC: 864 AN: 1456466 Hom.: 0 Cov.: 29 AF XY: 0.000610 AC XY: 442 AN XY: 724926

African (AFR) AF: 0.000120 AC: 4 AN: 33344

American (AMR) AF: 0.000134 AC: 6 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86088

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.000737 AC: 816 AN: 1107420

Other (OTH) AF: 0.000498 AC: 30 AN: 60200

GnomAD4 genome AF: 0.000336 AC: 51 AN: 151890 Hom.: 1 Cov.: 32 AF XY: 0.000310 AC XY: 23 AN XY: 74176

African (AFR) AF: 0.0000725 AC: 3 AN: 41356

American (AMR) AF: 0.000131 AC: 2 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000677 AC: 46 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000534 Hom.: 0

Bravo AF: 0.000321

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000280 AC: 34

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.000832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.049
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		6.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.078
Sift	Benign	0.23	T
Sift4G	Benign	0.47	T
Polyphen		0.071	B
Vest4		0.28
MVP		0.36
MPC		0.74
ClinPred		0.032	T
GERP RS		5.8
gMVP		0.14
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs141557672; hg19: chr1-240964793; COSMIC: COSV100471562;