16-269515-T-G

Variant names:

• chr16-269515-T-G
• NM_183337.3:c.1277A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183337.3(RGS11):​c.1277A>C​(p.Glu426Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RGS11 NM_183337.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67

Genes affected

RGS11 (HGNC:9993): (regulator of G protein signaling 11) The protein encoded by this gene belongs to the RGS (regulator of G protein signaling) family. Members of the RGS family act as GTPase-activating proteins on the alpha subunits of heterotrimeric, signal-transducing G proteins. This protein inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Alternative splicing occurs at this locus and four transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2013]

FAM234A (HGNC:14163): (family with sequence similarity 234 member A) Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286901 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS11	NM_183337.3	c.1277A>C	p.Glu426Ala	missense_variant	Exon 16 of 17	ENST00000397770.8	NP_899180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS11	ENST00000397770.8	c.1277A>C	p.Glu426Ala	missense_variant	Exon 16 of 17	1	NM_183337.3	ENSP00000380876.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1277A>C (p.E426A) alteration is located in exon 16 (coding exon 16) of the RGS11 gene. This alteration results from a A to C substitution at nucleotide position 1277, causing the glutamic acid (E) at amino acid position 426 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.23
Sift	Benign	0.036	D;T;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.98	D;.;D
Vest4		0.45
MutPred		0.39		Loss of ubiquitination at K428 (P = 0.0318);.;.;
MVP		0.63
MPC		0.43
ClinPred		0.93	D
GERP RS		4.4
Varity_R		0.40
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-319514;