10-99330198-C-G

Variant names:

• chr10-99330198-C-G
• rs931737637
• NM_020348.3:c.811C>G

Variant summary

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

The NM_020348.3(CNNM1):​c.811C>G​(p.Arg271Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R271S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNNM1 NM_020348.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

CNNM1 (HGNC:102): (cyclin and CBS domain divalent metal cation transport mediator 1) This gene encodes a member of the ancient conserved domain protein family. The encoded protein may bind copper. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

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_020348.3. 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
	CNNM1	NM_020348.3	MANE Select	c.811C>G	p.Arg271Gly	missense	Exon 1 of 11	NP_065081.2	Q9NRU3-1
	CNNM1	NM_001345887.2		c.811C>G	p.Arg271Gly	missense	Exon 1 of 12	NP_001332816.1	A0A8Q3SIV9
	CNNM1	NM_001345889.2		c.811C>G	p.Arg271Gly	missense	Exon 1 of 11	NP_001332818.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM1	ENST00000356713.5	TSL:1 MANE Select	c.811C>G	p.Arg271Gly	missense	Exon 1 of 11	ENSP00000349147.4	Q9NRU3-1
	CNNM1	ENST00000696687.1		c.811C>G	p.Arg271Gly	missense	Exon 1 of 12	ENSP00000512809.1	A0A8Q3SIV9
	CNNM1	ENST00000914274.1		c.811C>G	p.Arg271Gly	missense	Exon 1 of 10	ENSP00000584333.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	2.0	M
PhyloP100		1.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.069	T
Polyphen		0.95	P
Vest4		0.33
MutPred		0.66		Loss of MoRF binding (P = 0.0318)
MVP		0.30
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.47
gMVP		0.67
Mutation Taster		=47/53	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

dbSNP: rs931737637; hg19: chr10-101089955;