Genetic Variant RGS17:p.Pro13Thr (chr6-153043982-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.37C>A(p.Pro13Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,660 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. P13A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RGS17
NM_012419.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.29

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=0.16343981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5 link	c.37C>A	p.Pro13Thr	missense_variant	Exon 2 of 5	ENST00000206262.2	NP_036551.3	Q9UGC6
RGS17	XM_047418634.1 link	c.82C>A	p.Pro28Thr	missense_variant	Exon 2 of 5		XP_047274590.1
RGS17	XM_047418635.1 link	c.70C>A	p.Pro24Thr	missense_variant	Exon 2 of 5		XP_047274591.1
RGS17	XM_047418636.1 link	c.37C>A	p.Pro13Thr	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.37C>A	p.Pro13Thr	missense_variant	Exon 2 of 5	1	NM_012419.5	ENSP00000206262.1		Q9UGC6
RGS17	ENST00000367225.6 link	c.37C>A	p.Pro13Thr	missense_variant	Exon 1 of 4	1		ENSP00000356194.1		Q9UGC6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726670

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33364

American (AMR)

AF:

0.00

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.00

AC:

AN:

86102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111398

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

0.055

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.39

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.043

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.4

L;L

PhyloP100

4.3

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.0020

B;B

Vest4

0.22

MutPred

0.17

Loss of phosphorylation at T12 (P = 0.0464);Loss of phosphorylation at T12 (P = 0.0464);

MVP

0.52

MPC

0.44

ClinPred

0.44

GERP RS

4.2

PromoterAI

0.060

Neutral

(source)

Varity_R

0.12

gMVP

0.37

Mutation Taster

=74/26

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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6-153043982-G-T

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