chr9-35546656-C-T

Variant names:

• chr9-35546656-C-T
• rs1200848622
• NM_014806.5:c.135C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_014806.5(RUSC2):​c.135C>T​(p.Phe45Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000636 in 1,571,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: RUSC2 NM_014806.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.31
• Publications: 1 publications found

Genes affected

RUSC2 (HGNC:23625): (RUN and SH3 domain containing 2) This gene encodes a RUN and SH3 domain containing protein that interacts with Rab1b and Rab1-binding protein GM130. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jun 2012]

RUSC2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 61

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), PanelApp Australia

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=-0.41).
• BP6: Variant 9-35546656-C-T is Benign according to our data. Variant chr9-35546656-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1900766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.31 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014806.5. 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
	RUSC2	NM_014806.5	MANE Select	c.135C>T	p.Phe45Phe	synonymous	Exon 2 of 12	NP_055621.2	Q8N2Y8
	RUSC2	NM_001135999.2		c.135C>T	p.Phe45Phe	synonymous	Exon 2 of 12	NP_001129471.2	Q8N2Y8
	RUSC2	NM_001330740.2		c.-620-8404C>T		intron	N/A	NP_001317669.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUSC2	ENST00000361226.8	TSL:2 MANE Select	c.135C>T	p.Phe45Phe	synonymous	Exon 2 of 12	ENSP00000355177.3	Q8N2Y8
	RUSC2	ENST00000455600.1	TSL:1	c.135C>T	p.Phe45Phe	synonymous	Exon 2 of 12	ENSP00000393922.1	Q8N2Y8
	RUSC2	ENST00000866950.1		c.135C>T	p.Phe45Phe	synonymous	Exon 2 of 12	ENSP00000537009.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000466 AC: 1 AN: 214712 AF XY: 0.00000874

Gnomad AFR exome AF: 0.0000629

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000564 AC: 8 AN: 1419422 Hom.: 0 Cov.: 29 AF XY: 0.00000712 AC XY: 5 AN XY: 702030

African (AFR) AF: 0.0000308 AC: 1 AN: 32468

American (AMR) AF: 0.00 AC: 0 AN: 38828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.00 AC: 0 AN: 78174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5548

European-Non Finnish (NFE) AF: 0.00000550 AC: 6 AN: 1091642

Other (OTH) AF: 0.0000171 AC: 1 AN: 58516

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		3.3

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

Other links and lift over

dbSNP: rs1200848622; hg19: chr9-35546653;