9-133098621-T-C

Position:

• chr9-133098621-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000372050.8(RALGDS):​c.2711A>G​(p.Gln904Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: RALGDS ENST00000372050.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61

Genes affected

RALGDS (HGNC:9842): (ral guanine nucleotide dissociation stimulator) Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes.[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3146519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGDS	NM_006266.4	c.2711A>G	p.Gln904Arg	missense_variant	18/18	ENST00000372050.8	NP_006257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGDS	ENST00000372050.8	c.2711A>G	p.Gln904Arg	missense_variant	18/18	1	NM_006266.4	ENSP00000361120	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.2711A>G (p.Q904R) alteration is located in exon 18 (coding exon 18) of the RALGDS gene. This alteration results from a A to G substitution at nucleotide position 2711, causing the glutamine (Q) at amino acid position 904 to be replaced by an arginine (R). 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	0.26
BayesDel_addAF	Benign	0.0091	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.;.;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.31	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M;.;.;.;.;.
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.3	N;N;N;N;N;.
REVEL	Benign	0.17
Sift	Benign	0.14	T;T;T;T;T;.
Sift4G	Benign	0.098	T;T;T;T;T;.
Polyphen		0.13	B;.;.;.;.;.
Vest4		0.53
MutPred		0.24		.;.;.;.;.;Gain of methylation at K979 (P = 0.0544);
MVP		0.64
MPC		0.34
ClinPred		0.83	D
GERP RS		2.9
Varity_R		0.098
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-135974008;