18-23503683-C-T

Variant names:

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

Variant summary

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

The NM_013326.5(RMC1):​c.65C>T​(p.Pro22Leu) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P22H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RMC1 NM_013326.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• Publications: 5 publications found

Genes affected

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

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=0.16719502).

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 236056 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 30630

American (AMR) AF: 0.00 AC: 0 AN: 43162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25442

East Asian (EAS) AF: 0.00 AC: 0 AN: 37300

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102882

Other (OTH) AF: 0.00 AC: 0 AN: 59290

GnomAD4 genome Cov.: 33

Alfa AF: 0.00000591 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
PhyloP100		4.2
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
PromoterAI		0.074	Neutral
Varity_R		0.18
gMVP		0.19
Mutation Taster		=83/17	polymorphism

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

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