11-32097191-C-T

Variant names:

• chr11-32097191-C-T
• NM_002901.4:c.302C>T

Variant summary

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

The NM_002901.4(RCN1):​c.302C>T​(p.Thr101Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T101S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RCN1 NM_002901.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97
• Publications: 0 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002901.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCN1	NM_002901.4	MANE Select	c.302C>T	p.Thr101Ile	missense	Exon 2 of 6	NP_002892.1	Q15293-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCN1	ENST00000054950.4	TSL:1 MANE Select	c.302C>T	p.Thr101Ile	missense	Exon 2 of 6	ENSP00000054950.4	Q15293-1
	ENSG00000285283	ENST00000532942.5	TSL:2	c.149C>T	p.Thr50Ile	missense	Exon 2 of 6	ENSP00000436422.1
	ENSG00000285283	ENST00000530348.5	TSL:4	c.-197C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000436482.1	E9PP27

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Benign	0.015
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Benign	0.18	T
Sift4G	Benign	0.16	T
Polyphen		0.0070	B
Vest4		0.66
MutPred		0.33		Loss of catalytic residue at T101 (P = 0.041)
MVP		0.76
MPC		0.52
ClinPred		0.89	D
GERP RS		4.1
Varity_R		0.27
gMVP		0.49
Mutation Taster		=38/62	disease causing

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

Other links and lift over

hg19: chr11-32118737;