chr1-155325611-C-T

Variant names:

• chr1-155325611-C-T
• rs1651290708
• ENST00000490373.5:c.-321C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000490373.5(RUSC1):​c.-321C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,490 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RUSC1 ENST00000490373.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34845418).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490373.5. 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
	RUSC1	NM_001105203.2	MANE Select	c.1753C>T	p.Arg585Cys	missense	Exon 6 of 10	NP_001098673.1	Q9BVN2-1
	RUSC1	NM_001105204.2		c.1753C>T	p.Arg585Cys	missense	Exon 6 of 10	NP_001098674.1	Q9BVN2-4
	RUSC1	NM_001105205.1		c.523C>T	p.Arg175Cys	missense	Exon 5 of 9	NP_001098675.1	Q9BVN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUSC1	ENST00000490373.5	TSL:1	c.-321C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 8	ENSP00000484026.1	Q68CX2
	RUSC1	ENST00000471876.5	TSL:1	c.-255C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 8	ENSP00000482409.1	A0A087WZ68
	RUSC1	ENST00000368352.10	TSL:2 MANE Select	c.1753C>T	p.Arg585Cys	missense	Exon 6 of 10	ENSP00000357336.5	Q9BVN2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460490 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726586

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.0030
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.7
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.33
MutPred		0.59		Loss of MoRF binding (P = 0.0089)
MVP		0.50
MPC		1.0
ClinPred		0.98	D
GERP RS		3.4
PromoterAI		0.050	Neutral
Varity_R		0.49
gMVP		0.25
Mutation Taster		=59/41	polymorphism

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: rs1651290708; hg19: chr1-155295402;