1-155324874-C-G

Variant names:

• chr1-155324874-C-G
• rs368933433
• NM_001105203.2:c.1387C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105203.2(RUSC1):​c.1387C>G​(p.Pro463Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P463L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: RUSC1 NM_001105203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.253
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08059478).

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.1387C>G	p.Pro463Ala	missense	Exon 3 of 10	NP_001098673.1	Q9BVN2-1
	RUSC1	NM_001105204.2		c.1387C>G	p.Pro463Ala	missense	Exon 3 of 10	NP_001098674.1	Q9BVN2-4
	RUSC1	NM_001105205.1		c.157C>G	p.Pro53Ala	missense	Exon 2 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.1387C>G	p.Pro463Ala	missense	Exon 3 of 10	ENSP00000357336.5	Q9BVN2-1
	RUSC1	ENST00000368347.8	TSL:1	c.157C>G	p.Pro53Ala	missense	Exon 2 of 9	ENSP00000357331.4	Q9BVN2-3
	RUSC1	ENST00000292254.8	TSL:1	c.-21C>G		5_prime_UTR	Exon 1 of 8	ENSP00000292254.4	Q9BVN2-2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152226 Hom.: 0 Cov.: 34

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251366 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000465 AC: 68 AN: 1461886 Hom.: 0 Cov.: 72 AF XY: 0.0000399 AC XY: 29 AN XY: 727246

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

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1112008

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152226 Hom.: 0 Cov.: 34 AF XY: 0.0000672 AC XY: 5 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000301 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.093
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.25
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.028
Sift	Benign	0.060	T
Sift4G	Benign	0.21	T
Polyphen		0.073	B
Vest4		0.35
MVP		0.35
MPC		0.91
ClinPred		0.050	T
GERP RS		2.8
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.054
gMVP		0.15
Mutation Taster		=89/11	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: rs368933433; hg19: chr1-155294665;