Variant 15-90957205-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001017919.2(RCCD1):c.259C>T(p.Arg87Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,406,734 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 1 hom. )

Consequence

RCCD1
NM_001017919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.817

Variant links:

Genes affected

RCCD1 (HGNC:30457): (RCC1 domain containing 1) Predicted to be involved in chromatin organization. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RCCD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035183698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCCD1	NM_001017919.2 link	c.259C>T	p.Arg87Cys	missense_variant	3/8	ENST00000394258.7	NP_001017919.1	A6NED2A0A024RC72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCCD1	ENST00000394258.7 link	c.259C>T	p.Arg87Cys	missense_variant	3/8	1	NM_001017919.2	ENSP00000377801.2		A6NED2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

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:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000166

AC:

AN:

30046

Hom.:

AF XY:

0.000253

AC XY:

AN XY:

15792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000694

AC:

AN:

1254462

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

607850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000386

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000121

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.259C>T (p.R87C) alteration is located in exon 4 (coding exon 2) of the RCCD1 gene. This alteration results from a C to T substitution at nucleotide position 259, causing the arginine (R) at amino acid position 87 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.76

.;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;M

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.049

Sift

Uncertain

0.0080

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.46

P;P;P

Vest4

0.24

MutPred

0.48

Loss of disorder (P = 0.057);Loss of disorder (P = 0.057);Loss of disorder (P = 0.057);

MVP

0.34

MPC

1.3

ClinPred

0.070

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.16

gMVP

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over