2-96816291-T-G

Variant names:

• chr2-96816291-T-G
• rs775001414
• NM_017623.5:c.14T>G

Variant summary

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

The NM_017623.5(CNNM3):​c.14T>G​(p.Val5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. V5A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNNM3 NM_017623.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0897989).

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.14T>G	p.Val5Gly	missense	Exon 1 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.14T>G	p.Val5Gly	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.14T>G	p.Val5Gly	missense	Exon 1 of 8	ENSP00000305449.3	Q8NE01-1
	CNNM3	ENST00000947263.1		c.14T>G	p.Val5Gly	missense	Exon 1 of 8	ENSP00000617322.1
	CNNM3	ENST00000947265.1		c.14T>G	p.Val5Gly	missense	Exon 1 of 8	ENSP00000617324.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.16	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.31
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.15	N
REVEL	Benign	0.20
Sift	Benign	0.047	D
Sift4G	Uncertain	0.014	D
Polyphen		0.0	B
Vest4		0.15
MutPred		0.42		Gain of disorder (P = 0.017)
MVP		0.12
ClinPred		0.11	T
GERP RS		-1.5
PromoterAI		-0.055	Neutral
Varity_R		0.060
gMVP		0.38
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775001414; hg19: chr2-97482028;