16-269557-T-A

Variant names:

• chr16-269557-T-A
• rs2051821712
• NM_183337.3:c.1235A>T

Variant summary

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

The NM_183337.3(RGS11):​c.1235A>T​(p.Asp412Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.45

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.1235A>T	p.Asp412Val	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.1235A>T	p.Asp412Val	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

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1235A>T (p.D412V) alteration is located in exon 16 (coding exon 16) of the RGS11 gene. This alteration results from a A to T substitution at nucleotide position 1235, causing the aspartic acid (D) at amino acid position 412 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.022
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.3	M;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D;D;D
Sift4G	Benign	0.061	T;T;D
Polyphen		0.99	D;.;D
Vest4		0.55
MutPred		0.51		Gain of MoRF binding (P = 0.0234);.;.;
MVP		0.58
MPC		0.53
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.50
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2051821712; hg19: chr16-319556;