6-153026512-T-A

Variant names:

• chr6-153026512-T-A
• rs761548542
• NM_012419.5:c.151A>T

Variant summary

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

The NM_012419.5(RGS17):​c.151A>T​(p.Asn51Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. N51D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS17 NM_012419.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 1 publications found

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]

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=0.12666121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS17	NM_012419.5	c.151A>T	p.Asn51Tyr	missense_variant	Exon 3 of 5	ENST00000206262.2	NP_036551.3
RGS17	XM_047418634.1	c.196A>T	p.Asn66Tyr	missense_variant	Exon 3 of 5		XP_047274590.1
RGS17	XM_047418635.1	c.184A>T	p.Asn62Tyr	missense_variant	Exon 3 of 5		XP_047274591.1
RGS17	XM_047418636.1	c.151A>T	p.Asn51Tyr	missense_variant	Exon 3 of 5		XP_047274592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS17	ENST00000206262.2	c.151A>T	p.Asn51Tyr	missense_variant	Exon 3 of 5	1	NM_012419.5	ENSP00000206262.1
RGS17	ENST00000367225.6	c.151A>T	p.Asn51Tyr	missense_variant	Exon 2 of 4	1		ENSP00000356194.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;L
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.052
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.40	B;B
Vest4		0.46
MutPred		0.25		Gain of phosphorylation at N51 (P = 0.0472);Gain of phosphorylation at N51 (P = 0.0472);
MVP		0.47
MPC		0.49
ClinPred		0.38	T
GERP RS		4.0
Varity_R		0.074
gMVP		0.22
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs761548542; hg19: chr6-153347647;