NM_001017919.2:c.299C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001017919.2(RCCD1):​c.299C>T​(p.Ala100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,315,376 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A100E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RCCD1 NM_001017919.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04406795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCCD1	NM_001017919.2	c.299C>T	p.Ala100Val	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>T	p.Ala100Val	missense_variant	Exon 3 of 8	1	NM_001017919.2	ENSP00000377801.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1315376 Hom.: 0 Cov.: 32 AF XY: 0.00000156 AC XY: 1 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: 0.0000498 AC: 1 AN: 20086

East Asian (EAS) AF: 0.00 AC: 0 AN: 33276

South Asian (SAS) AF: 0.00 AC: 0 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: 9.63e-7 AC: 1 AN: 1038620

Other (OTH) AF: 0.00 AC: 0 AN: 54424

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.6
DANN	Benign	0.96
DEOGEN2	Benign	0.0067	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.55	.;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;L
PhyloP100		-0.24
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.98	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0070	B;B;B
Vest4		0.091
MutPred		0.44		Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);
MVP		0.014
MPC		0.88
ClinPred		0.071	T
GERP RS		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.029
gMVP		0.43

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;