15-90956764-C-A

Position:

• chr15-90956764-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001017919.2(RCCD1):​c.30C>A​(p.Phe10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RCCD1 NM_001017919.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0910

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCCD1	NM_001017919.2	c.30C>A	p.Phe10Leu	missense_variant	2/8	ENST00000394258.7	NP_001017919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCCD1	ENST00000394258.7	c.30C>A	p.Phe10Leu	missense_variant	2/8	1	NM_001017919.2	ENSP00000377801.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1177842 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 569968

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.30C>A (p.F10L) alteration is located in exon 3 (coding exon 1) of the RCCD1 gene. This alteration results from a C to A substitution at nucleotide position 30, causing the phenylalanine (F) at amino acid position 10 to be replaced by a leucine (L). 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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0064	T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.73	.;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	0.054	D
MutationAssessor	Uncertain	2.3	M;.;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.89	N;N;N
REVEL	Uncertain	0.56
Sift	Uncertain	0.018	D;D;D
Sift4G	Uncertain	0.026	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.54
MutPred		0.69		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.76
MPC		1.4
ClinPred		0.82	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.32
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-91499994;