Variant 15-90957238-G-A 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.292G>A(p.Val98Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,462,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

RCCD1
NM_001017919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.923

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:

RCCD1 (HGNC:):

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=0.014546782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCCD1	NM_001017919.2 linkuse as main transcript	c.292G>A	p.Val98Ile	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 linkuse as main transcript	c.292G>A	p.Val98Ile	missense_variant	3/8	1	NM_001017919.2	ENSP00000377801.2		A6NED2

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000508

AC:

AN:

80740

Hom.:

AF XY:

0.000379

AC XY:

AN XY:

42172

show subpopulations

Gnomad AFR exome

AF:

0.000692

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.000362

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000942

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000337

Gnomad OTH exome

AF:

0.00121

GnomAD4 exome

AF:

0.000332

AC:

435

AN:

1310598

Hom.:

Cov.:

AF XY:

0.000317

AC XY:

202

AN XY:

637740

show subpopulations

Gnomad4 AFR exome

AF:

0.000949

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.000101

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000298

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000289

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000597

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000601

Hom.:

Bravo

AF:

0.000774

ESP6500AA

AF:

0.000258

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000228

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3472

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

Jul 20, 2021

The c.292G>A (p.V98I) alteration is located in exon 4 (coding exon 2) of the RCCD1 gene. This alteration results from a G to A substitution at nucleotide position 292, causing the valine (V) at amino acid position 98 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0037

T;T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.39

.;T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

N;.;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.19

N;N;N

REVEL

Benign

0.042

Sift

Uncertain

0.016

D;D;D

Sift4G

Benign

0.43

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.037

MVP

0.048

MPC

0.72

ClinPred

0.012

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.075

gMVP

0.21

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