18-23503683-C-T

Variant names:

• chr18-23503683-C-T
• rs112277818
• NM_013326.5:c.65C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318707.1(RMC1):​c.-178C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000208 in 1,442,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RMC1 NM_001318707.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21

Genes affected

RMC1 (HGNC:24326): (regulator of MON1-CCZ1) This gene encodes a colon cancer associated protein. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16719502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMC1	NM_013326.5	c.65C>T	p.Pro22Leu	missense_variant	Exon 1 of 20	ENST00000269221.8	NP_037458.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMC1	ENST00000269221.8	c.65C>T	p.Pro22Leu	missense_variant	Exon 1 of 20	1	NM_013326.5	ENSP00000269221.2
RMC1	ENST00000590868.5	c.65C>T	p.Pro22Leu	missense_variant	Exon 1 of 18	2		ENSP00000467007.1
RMC1	ENST00000615148.5	c.65C>T	p.Pro22Leu	missense_variant	Exon 1 of 20	5		ENSP00000482573.2
RMC1	ENST00000589215.5	n.65C>T		non_coding_transcript_exon_variant	Exon 1 of 19	2		ENSP00000467852.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1442174 Hom.: 0 Cov.: 31 AF XY: 0.00000418 AC XY: 3 AN XY: 717720

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.00000883 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.073
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.4	.;N;.
REVEL	Benign	0.033
Sift	Benign	0.30	.;T;.
Sift4G	Benign	0.24	T;T;T
Polyphen		0.085	.;B;.
Vest4		0.37
MutPred		0.33		Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);
MVP		0.093
MPC		0.40
ClinPred		0.53	D
GERP RS		3.7
Varity_R		0.18
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs112277818; hg19: chr18-21083647; COSMIC: COSV52574154; COSMIC: COSV52574154;