chr11-32098358-G-T

Variant names:

• chr11-32098358-G-T
• rs117017377
• NM_002901.4:c.457G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002901.4(RCN1):​c.457G>T​(p.Ala153Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. A153T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCN1 NM_002901.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40
• Publications: 6 publications found

Genes affected

RCN1 (HGNC:9934): (reticulocalbin 1) Reticulocalbin 1 is a calcium-binding protein located in the lumen of the ER. The protein contains six conserved regions with similarity to a high affinity Ca(+2)-binding motif, the EF-hand. High conservation of amino acid residues outside of these motifs, in comparison to mouse reticulocalbin, is consistent with a possible biochemical function besides that of calcium binding. In human endothelial and prostate cancer cell lines this protein localizes to the plasma membrane.[provided by RefSeq, Jan 2009]

ENSG00000285283 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07320207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCN1	NM_002901.4	c.457G>T	p.Ala153Ser	missense_variant	Exon 3 of 6	ENST00000054950.4	NP_002892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCN1	ENST00000054950.4	c.457G>T	p.Ala153Ser	missense_variant	Exon 3 of 6	1	NM_002901.4	ENSP00000054950.4
ENSG00000285283	ENST00000532942.5	c.304G>T	p.Ala102Ser	missense_variant	Exon 3 of 6	2		ENSP00000436422.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.050	.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.77
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L
PhyloP100		3.4
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.10	N;N
REVEL	Benign	0.15
Sift	Benign	0.67	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.0080	.;B
Vest4		0.18
MutPred		0.22		.;Gain of disorder (P = 0.0359);
MVP		0.39
MPC		0.43
ClinPred		0.097	T
GERP RS		0.35
Varity_R		0.049
gMVP		0.32
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs117017377; hg19: chr11-32119904;