rs41264941

Variant names:

• chr1-155321986-C-A
• rs41264941
• NM_001105203.2:c.213C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-155321986-C-A
• chr1-155321986-C-T

Variant summary

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

The NM_001105203.2(RUSC1):​c.213C>A​(p.Cys71*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C71C) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RUSC1 NM_001105203.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• 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]

RUSC1-AS1 (HGNC:26680): (RUSC1 antisense RNA 1)

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_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.213C>A	p.Cys71*	stop_gained	Exon 2 of 10	NP_001098673.1	Q9BVN2-1
	RUSC1	NM_001105204.2		c.213C>A	p.Cys71*	stop_gained	Exon 2 of 10	NP_001098674.1	Q9BVN2-4
	RUSC1-AS1	NR_145424.1		n.294+257G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUSC1	ENST00000368352.10	TSL:2 MANE Select	c.213C>A	p.Cys71*	stop_gained	Exon 2 of 10	ENSP00000357336.5	Q9BVN2-1
	RUSC1-AS1	ENST00000450199.2	TSL:1	n.264-291G>T		intron	N/A
	RUSC1	ENST00000696599.1		c.213C>A	p.Cys71*	stop_gained	Exon 2 of 11	ENSP00000512744.1	A0A8Q3SIT1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446870 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 718490

African (AFR) AF: 0.00 AC: 0 AN: 33208

American (AMR) AF: 0.00 AC: 0 AN: 43422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24776

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 84180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103704

Other (OTH) AF: 0.00 AC: 0 AN: 59744

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.75	D
PhyloP100		0.98
Vest4		0.27
GERP RS		2.6
Mutation Taster		=16/184	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs41264941; hg19: chr1-155291777;