1-155325142-C-A

Variant names:

• chr1-155325142-C-A
• rs376024390
• NM_001105203.2:c.1497C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001105203.2(RUSC1):​c.1497C>A​(p.Ile499Ile) 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: RUSC1 NM_001105203.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 1 publications found

Genes affected

RUSC1 (HGNC:17153): (RUN and SH3 domain containing 1) Predicted to enable actin binding activity. Involved in protein polyubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.443 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105203.2. 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
	RUSC1	NM_001105203.2	MANE Select	c.1497C>A	p.Ile499Ile	synonymous	Exon 4 of 10	NP_001098673.1	Q9BVN2-1
	RUSC1	NM_001105204.2		c.1497C>A	p.Ile499Ile	synonymous	Exon 4 of 10	NP_001098674.1	Q9BVN2-4
	RUSC1	NM_001105205.1		c.267C>A	p.Ile89Ile	synonymous	Exon 3 of 9	NP_001098675.1	Q9BVN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUSC1	ENST00000368352.10	TSL:2 MANE Select	c.1497C>A	p.Ile499Ile	synonymous	Exon 4 of 10	ENSP00000357336.5	Q9BVN2-1
	RUSC1	ENST00000368347.8	TSL:1	c.267C>A	p.Ile89Ile	synonymous	Exon 3 of 9	ENSP00000357331.4	Q9BVN2-3
	RUSC1	ENST00000292254.8	TSL:1	c.90C>A	p.Ile30Ile	synonymous	Exon 2 of 8	ENSP00000292254.4	Q9BVN2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.44
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs376024390; hg19: chr1-155294933;