1-155321986-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001105203.2(RUSC1):​c.213C>T​(p.Cys71Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,599,180 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: RUSC1 NM_001105203.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.978
• 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]

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

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-155321986-C-T is Benign according to our data. Variant chr1-155321986-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.978 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.213C>T	p.Cys71Cys	synonymous	Exon 2 of 10	NP_001098673.1	Q9BVN2-1
	RUSC1	NM_001105204.2		c.213C>T	p.Cys71Cys	synonymous	Exon 2 of 10	NP_001098674.1	Q9BVN2-4
	RUSC1-AS1	NR_145424.1		n.294+257G>A		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>T	p.Cys71Cys	synonymous	Exon 2 of 10	ENSP00000357336.5	Q9BVN2-1
	RUSC1-AS1	ENST00000450199.2	TSL:1	n.264-291G>A		intron	N/A
	RUSC1	ENST00000696599.1		c.213C>T	p.Cys71Cys	synonymous	Exon 2 of 11	ENSP00000512744.1	A0A8Q3SIT1

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000423 AC: 99 AN: 234158 AF XY: 0.000535

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000243

Gnomad ASJ exome AF: 0.000355

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000690

Gnomad OTH exome AF: 0.00176

GnomAD4 exome AF: 0.000297 AC: 430 AN: 1446868 Hom.: 1 Cov.: 32 AF XY: 0.000320 AC XY: 230 AN XY: 718488

African (AFR) AF: 0.0000903 AC: 3 AN: 33208

American (AMR) AF: 0.000299 AC: 13 AN: 43422

Ashkenazi Jewish (ASJ) AF: 0.000202 AC: 5 AN: 24776

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39570

South Asian (SAS) AF: 0.000131 AC: 11 AN: 84180

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

Middle Eastern (MID) AF: 0.00527 AC: 30 AN: 5688

European-Non Finnish (NFE) AF: 0.000311 AC: 343 AN: 1103702

Other (OTH) AF: 0.000402 AC: 24 AN: 59744

GnomAD4 genome AF: 0.000374 AC: 57 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74474

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00157 AC: 24 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000441 Hom.: 0

Bravo AF: 0.000484

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	-0.57
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		0.98
Mutation Taster		=100/0	polymorphism

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;