rs202063703

Variant names:

• chr15-90957245-C-A
• rs202063703
• NM_001017919.2:c.299C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-90957245-C-A
• chr15-90957245-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001017919.2(RCCD1):​c.299C>A​(p.Ala100Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,467,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A100T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: RCCD1 NM_001017919.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.242
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009492934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCCD1	NM_001017919.2	c.299C>A	p.Ala100Glu	missense_variant	Exon 3 of 8	ENST00000394258.7	NP_001017919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCCD1	ENST00000394258.7	c.299C>A	p.Ala100Glu	missense_variant	Exon 3 of 8	1	NM_001017919.2	ENSP00000377801.2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

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: 0.0000824 AC: 7 AN: 84926 AF XY: 0.0000449

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000781

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000320

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 18 AN: 1315376 Hom.: 0 Cov.: 32 AF XY: 0.0000125 AC XY: 8 AN XY: 640394

African (AFR) AF: 0.00 AC: 0 AN: 27646

American (AMR) AF: 0.00 AC: 0 AN: 25942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20086

East Asian (EAS) AF: 0.000240 AC: 8 AN: 33276

South Asian (SAS) AF: 0.0000295 AC: 2 AN: 67894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5010

European-Non Finnish (NFE) AF: 0.00000578 AC: 6 AN: 1038620

Other (OTH) AF: 0.0000367 AC: 2 AN: 54424

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.000113 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.299C>A (p.A100E) alteration is located in exon 4 (coding exon 2) of the RCCD1 gene. This alteration results from a C to A substitution at nucleotide position 299, causing the alanine (A) at amino acid position 100 to be replaced by a glutamic acid (E). 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	-0.53	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.9
DANN	Benign	0.85
DEOGEN2	Benign	0.0050	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.54	.;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.0095	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;L
PhyloP100		-0.24
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.021
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.030	B;B;B
Vest4		0.15
MVP		0.014
MPC		1.0
ClinPred		0.018	T
GERP RS		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.067
gMVP		0.68
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs202063703; hg19: chr15-91500475;