Genetic Variant RUSC1:p.Gln510His (chr1-155325175-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001105203.2(RUSC1):c.1530G>C(p.Gln510His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,870 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: 6.8e-7 ( 0 hom. )

Consequence

RUSC1
NM_001105203.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

Publications

1 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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=0.3224696).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUSC1	NM_001105203.2	MANE Select	c.1530G>C	p.Gln510His	missense	Exon 4 of 10	NP_001098673.1	Q9BVN2-1
RUSC1	NM_001105204.2		c.1530G>C	p.Gln510His	missense	Exon 4 of 10	NP_001098674.1	Q9BVN2-4
RUSC1	NM_001105205.1		c.300G>C	p.Gln100His	missense	Exon 3 of 9	NP_001098675.1	Q9BVN2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUSC1	ENST00000368352.10	TSL:2 MANE Select	c.1530G>C	p.Gln510His	missense	Exon 4 of 10	ENSP00000357336.5	Q9BVN2-1
RUSC1	ENST00000368347.8	TSL:1	c.300G>C	p.Gln100His	missense	Exon 3 of 9	ENSP00000357331.4	Q9BVN2-3
RUSC1	ENST00000292254.8	TSL:1	c.123G>C	p.Gln41His	missense	Exon 2 of 8	ENSP00000292254.4	Q9BVN2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.84

M_CAP

Benign

0.022

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

PhyloP100

4.6

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.10

Sift

Uncertain

0.016

Sift4G

Uncertain

0.015

Polyphen

0.99

Vest4

0.32

MutPred

0.29

Loss of helix (P = 0.0558)

MVP

0.68

MPC

1.7

ClinPred

0.99

GERP RS

1.9

PromoterAI

-0.0070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.68

gMVP

0.47

Mutation Taster

=61/39

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over