rs1378760263

Variant names:

• chr2-96816363-C-G
• rs1378760263
• NM_017623.5:c.86C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-96816363-C-G
• chr2-96816363-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017623.5(CNNM3):​c.86C>G​(p.Pro29Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,165,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. P29L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CNNM3 NM_017623.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28435817).

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.86C>G	p.Pro29Arg	missense	Exon 1 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.86C>G	p.Pro29Arg	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.86C>G	p.Pro29Arg	missense	Exon 1 of 8	ENSP00000305449.3	Q8NE01-1
	CNNM3	ENST00000947263.1		c.86C>G	p.Pro29Arg	missense	Exon 1 of 8	ENSP00000617322.1
	CNNM3	ENST00000947265.1		c.86C>G	p.Pro29Arg	missense	Exon 1 of 8	ENSP00000617324.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 4 AN: 1165048 Hom.: 0 Cov.: 31 AF XY: 0.00000534 AC XY: 3 AN XY: 561766

African (AFR) AF: 0.00 AC: 0 AN: 23352

American (AMR) AF: 0.00 AC: 0 AN: 8828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15684

East Asian (EAS) AF: 0.00 AC: 0 AN: 26924

South Asian (SAS) AF: 0.00 AC: 0 AN: 43646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3326

European-Non Finnish (NFE) AF: 0.00000415 AC: 4 AN: 964634

Other (OTH) AF: 0.00 AC: 0 AN: 46890

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.0059	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.43
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.21	T
Polyphen		0.97	D
Vest4		0.12
MutPred		0.29		Gain of helix (P = 0.0117)
MVP		0.27
ClinPred		0.38	T
GERP RS		3.3
PromoterAI		-0.011	Neutral
Varity_R		0.081
gMVP		0.11
Mutation Taster		=94/6	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: rs1378760263; hg19: chr2-97482100;