Variant 15-90957231-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001017919.2(RCCD1):c.285A>C(p.Leu95Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,431,814 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RCCD1
NM_001017919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.107

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09351376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCCD1	NM_001017919.2 linkuse as main transcript	c.285A>C	p.Leu95Phe	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.285A>C	p.Leu95Phe	missense_variant	3/8	1	NM_001017919.2	ENSP00000377801.2		A6NED2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1279686

Hom.:

Cov.:

AF XY:

0.00000805

AC XY:

AN XY:

620978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000976

Gnomad4 OTH exome

AF:

0.0000379

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

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

Oct 21, 2024

The c.285A>C (p.L95F) alteration is located in exon 4 (coding exon 2) of the RCCD1 gene. This alteration results from a A to C substitution at nucleotide position 285, causing the leucine (L) at amino acid position 95 to be replaced by a phenylalanine (F). 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

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.011

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.47

.;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.094

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

L;.;L

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.072

Sift

Benign

0.37

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.79

P;P;P

Vest4

0.12

MutPred

0.35

Gain of catalytic residue at L95 (P = 0.0508);Gain of catalytic residue at L95 (P = 0.0508);Gain of catalytic residue at L95 (P = 0.0508);

MVP

0.067

MPC

1.3

ClinPred

0.32

GERP RS

-4.7

Varity_R

0.037

gMVP

0.36

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