chr9-133098713-G-T

Variant names:

• chr9-133098713-G-T
• rs886017
• NM_006266.4:c.2619C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006266.4(RALGDS):​c.2619C>A​(p.Thr873Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RALGDS NM_006266.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 23 publications found

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]

RALGDS Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000285245 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALGDS	NM_006266.4	MANE Select	c.2619C>A	p.Thr873Thr	synonymous	Exon 18 of 18	NP_006257.1
	RALGDS	NM_001271775.2		c.2616C>A	p.Thr872Thr	synonymous	Exon 18 of 18	NP_001258704.1
	RALGDS	NM_001271776.2		c.2583C>A	p.Thr861Thr	synonymous	Exon 18 of 18	NP_001258705.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALGDS	ENST00000372050.8	TSL:1 MANE Select	c.2619C>A	p.Thr873Thr	synonymous	Exon 18 of 18	ENSP00000361120.3
	ENSG00000285245	ENST00000647146.1		c.2832C>A	p.Thr944Thr	synonymous	Exon 23 of 23	ENSP00000493691.1
	RALGDS	ENST00000372047.7	TSL:1	c.2583C>A	p.Thr861Thr	synonymous	Exon 18 of 18	ENSP00000361117.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.10
DANN	Benign	0.50
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs886017; hg19: chr9-135974100;