Genetic Variant NM_012419.5:c.53C>A (chr6-153043966-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012419.5(RGS17):c.53C>A(p.Ala18Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A18V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RGS17
NM_012419.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.40

Publications

0 publications found

Variant links:

Genes affected

RGS17 (HGNC:14088): (regulator of G protein signaling 17) This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]

RGS17 links:

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ACMG classification

Classification was made for transcript

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=0.15514615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5 link	c.53C>A	p.Ala18Asp	missense_variant	Exon 2 of 5	ENST00000206262.2	NP_036551.3	Q9UGC6
RGS17	XM_047418634.1 link	c.98C>A	p.Ala33Asp	missense_variant	Exon 2 of 5		XP_047274590.1
RGS17	XM_047418635.1 link	c.86C>A	p.Ala29Asp	missense_variant	Exon 2 of 5		XP_047274591.1
RGS17	XM_047418636.1 link	c.53C>A	p.Ala18Asp	missense_variant	Exon 2 of 5		XP_047274592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS17	ENST00000206262.2 link	c.53C>A	p.Ala18Asp	missense_variant	Exon 2 of 5	1	NM_012419.5	ENSP00000206262.1		Q9UGC6
RGS17	ENST00000367225.6 link	c.53C>A	p.Ala18Asp	missense_variant	Exon 1 of 4	1		ENSP00000356194.1		Q9UGC6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460852

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33358

American (AMR)

AF:

0.00

AC:

AN:

44576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.00

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111576

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.29

T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

4.4

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.16

Sift

Benign

0.062

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.011

B;B

Vest4

0.44

MutPred

0.10

Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);

MVP

0.44

MPC

0.59

ClinPred

0.44

GERP RS

3.5

PromoterAI

0.053

Neutral

(source)

Varity_R

0.21

gMVP

0.61

Mutation Taster

=51/49

polymorphism

(source)

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

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NM_012419.5:c.53C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over