dbSNP rs751292506: RCC1:p.Thr32Ala (chr1-28531823-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001381865.2(RCC1):c.94A>G(p.Thr32Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000321 in 1,557,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RCC1
NM_001381865.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

Publications

1 publications found

Variant links:

Genes affected

RCC1 (HGNC:1913): (regulator of chromosome condensation 1) Enables several functions, including guanyl-nucleotide exchange factor activity; nucleosomal DNA binding activity; and protein heterodimerization activity. Involved in several processes, including G1/S transition of mitotic cell cycle; regulation of mitotic nuclear division; and spindle organization. Located in chromatin; cytoplasm; and nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.13850406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCC1	NM_001381865.2 link	c.94A>G	p.Thr32Ala	missense_variant	Exon 6 of 13	ENST00000683442.1	NP_001368794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCC1	ENST00000683442.1 link	c.94A>G	p.Thr32Ala	missense_variant	Exon 6 of 13		NM_001381865.2	ENSP00000508074.1		P18754-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000204

AC:

AN:

196400

AF XY:

0.0000191

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.0000785

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1405612

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

695354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31486

American (AMR)

AF:

0.0000581

AC:

AN:

34420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21610

East Asian (EAS)

AF:

0.00

AC:

AN:

39504

South Asian (SAS)

AF:

0.00

AC:

AN:

75306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088512

Other (OTH)

AF:

0.00

AC:

AN:

58066

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

AF:

0.0000197

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.187A>G (p.T63A) alteration is located in exon 4 (coding exon 3) of the RCC1 gene. This alteration results from a A to G substitution at nucleotide position 187, causing the threonine (T) at amino acid position 63 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.;T;.;T;T;T;.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.92

D;.;D;D;.;D;.;D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.14

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.55

N;.;.;.;N;.;N;.;.;.

PhyloP100

4.1

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.6

N;.;N;.;N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.13

T;.;T;.;T;T;T;T;T;T

Sift4G

Benign

0.89

T;.;T;.;T;T;T;T;T;T

Polyphen

0.0020

B;B;.;.;B;.;B;B;.;.

Vest4

0.41

MVP

0.73

MPC

0.43

ClinPred

0.098

GERP RS

4.7

Varity_R

0.26

gMVP

0.44

Mutation Taster

=64/36

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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rs751292506

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over