rs886017

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006266.4(RALGDS):​c.2619C>T​(p.Thr873Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,613,596 control chromosomes in the GnomAD database, including 228,533 homozygotes. 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: 𝑓 0.47 (17998 hom., cov: 32)
  • Exomes 𝑓: 0.53 (210535 hom.)
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

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>T	p.Thr873Thr	synonymous	Exon 18 of 18	NP_006257.1
	RALGDS	NM_001271775.2		c.2616C>T	p.Thr872Thr	synonymous	Exon 18 of 18	NP_001258704.1
	RALGDS	NM_001271776.2		c.2583C>T	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>T	p.Thr873Thr	synonymous	Exon 18 of 18	ENSP00000361120.3
	ENSG00000285245	ENST00000647146.1		c.2832C>T	p.Thr944Thr	synonymous	Exon 23 of 23	ENSP00000493691.1
	RALGDS	ENST00000372047.7	TSL:1	c.2583C>T	p.Thr861Thr	synonymous	Exon 18 of 18	ENSP00000361117.3

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71858 AN: 151982 Hom.: 17990 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.467

GnomAD2 exomes AF: 0.545 AC: 136598 AN: 250712 AF XY: 0.553

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.575

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.626

Gnomad FIN exome AF: 0.544

Gnomad NFE exome AF: 0.534

Gnomad OTH exome AF: 0.541

GnomAD4 exome AF: 0.534 AC: 779784 AN: 1461496 Hom.: 210535 Cov.: 53 AF XY: 0.539 AC XY: 391577 AN XY: 727076

African (AFR) AF: 0.288 AC: 9645 AN: 33470

American (AMR) AF: 0.566 AC: 25326 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12349 AN: 26134

East Asian (EAS) AF: 0.589 AC: 23390 AN: 39700

South Asian (SAS) AF: 0.663 AC: 57201 AN: 86248

European-Finnish (FIN) AF: 0.548 AC: 29239 AN: 53374

Middle Eastern (MID) AF: 0.533 AC: 3073 AN: 5764

European-Non Finnish (NFE) AF: 0.529 AC: 587904 AN: 1111700

Other (OTH) AF: 0.524 AC: 31657 AN: 60386

GnomAD4 genome AF: 0.473 AC: 71893 AN: 152100 Hom.: 17998 Cov.: 32 AF XY: 0.478 AC XY: 35513 AN XY: 74360

African (AFR) AF: 0.299 AC: 12391 AN: 41508

American (AMR) AF: 0.518 AC: 7924 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1631 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3129 AN: 5138

South Asian (SAS) AF: 0.663 AC: 3198 AN: 4820

European-Finnish (FIN) AF: 0.534 AC: 5653 AN: 10592

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36308 AN: 67972

Other (OTH) AF: 0.470 AC: 991 AN: 2110

Alfa AF: 0.495 Hom.: 13583

Bravo AF: 0.460

Asia WGS AF: 0.602 AC: 2092 AN: 3478

EpiCase AF: 0.522

EpiControl AF: 0.526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.15
DANN	Benign	0.55
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs886017; hg19: chr9-135974100; COSMIC: COSV64426175; COSMIC: COSV64426175;