rs865847530

Variant names:

• chr2-96816842-C-A
• rs865847530
• NM_017623.5:c.565C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-96816842-C-A
• chr2-96816842-C-T

Variant summary

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

The NM_017623.5(CNNM3):​c.565C>A​(p.Arg189Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000111 in 904,116 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R189C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: CNNM3 NM_017623.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 0 publications found

Genes affected

CNNM3 (HGNC:104): (cyclin and CBS domain divalent metal cation transport mediator 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in ion transport; magnesium ion homeostasis; and transmembrane transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CNNM3-DT (HGNC:53592): (CNNM3 divergent transcript)

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_017623.5. 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
	CNNM3	NM_017623.5	MANE Select	c.565C>A	p.Arg189Ser	missense	Exon 1 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.565C>A	p.Arg189Ser	missense	Exon 1 of 7	NP_951060.1	Q8NE01-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM3	ENST00000305510.4	TSL:1 MANE Select	c.565C>A	p.Arg189Ser	missense	Exon 1 of 8	ENSP00000305449.3	Q8NE01-1
	CNNM3	ENST00000947263.1		c.565C>A	p.Arg189Ser	missense	Exon 1 of 8	ENSP00000617322.1
	CNNM3	ENST00000947265.1		c.565C>A	p.Arg189Ser	missense	Exon 1 of 8	ENSP00000617324.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000111 AC: 1 AN: 904116 Hom.: 0 Cov.: 30 AF XY: 0.00000235 AC XY: 1 AN XY: 425184

African (AFR) AF: 0.00 AC: 0 AN: 17172

American (AMR) AF: 0.00 AC: 0 AN: 3188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6940

East Asian (EAS) AF: 0.00 AC: 0 AN: 7348

South Asian (SAS) AF: 0.00 AC: 0 AN: 18180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1966

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 810532

Other (OTH) AF: 0.00 AC: 0 AN: 31420

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Benign	1.5	L
PhyloP100		0.63
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.52
Sift	Benign	0.17	T
Sift4G	Benign	0.18	T
Polyphen		0.99	D
Vest4		0.25
MutPred		0.55		Loss of MoRF binding (P = 0.0219)
MVP		0.35
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.40
gMVP		0.71
Mutation Taster		=61/39	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: rs865847530; hg19: chr2-97482579;