RALGDS p.Thr873Thr

Variant names:

• chr9-133098712-C-C
• NM_006266.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr9-133098713--
• chr9-133098713-G-A
• chr9-133098713-G-T
• chr9-133098713-G-C

Variant summary

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

The NM_006266.4(RALGDS):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALGDS	NM_006266.4	MANE Select	c.		exon_region	Exon 18 of 18	NP_006257.1	Q12967-1
	RALGDS	NM_001271775.2		c.		exon_region	Exon 18 of 18	NP_001258704.1	Q12967-5
	RALGDS	NM_001271776.2		c.		exon_region	Exon 18 of 18	NP_001258705.1	Q12967-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALGDS	ENST00000372050.8	TSL:1 MANE Select	c.		exon_region	Exon 18 of 18	ENSP00000361120.3	Q12967-1
	ENSG00000285245	ENST00000647146.1		c.		exon_region	Exon 23 of 23	ENSP00000493691.1	A0A2R8Y471
	RALGDS	ENST00000372047.7	TSL:1	c.		exon_region	Exon 18 of 18	ENSP00000361117.3	Q12967-6

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
PhyloP100		-2.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-135974099;