chr2-96816435-C-T

Variant names:

• chr2-96816435-C-T
• rs2079317690
• NM_017623.5:c.158C>T

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.158C>T​(p.Ala53Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,426 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CNNM3 NM_017623.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.246
• 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=0.119775176).

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.158C>T	p.Ala53Val	missense	Exon 1 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.158C>T	p.Ala53Val	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.158C>T	p.Ala53Val	missense	Exon 1 of 8	ENSP00000305449.3	Q8NE01-1
	CNNM3	ENST00000947263.1		c.158C>T	p.Ala53Val	missense	Exon 1 of 8	ENSP00000617322.1
	CNNM3	ENST00000947265.1		c.158C>T	p.Ala53Val	missense	Exon 1 of 8	ENSP00000617324.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151918 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000160 AC: 2 AN: 1246508 Hom.: 0 Cov.: 31 AF XY: 0.00000164 AC XY: 1 AN XY: 610420

African (AFR) AF: 0.00 AC: 0 AN: 24846

American (AMR) AF: 0.00 AC: 0 AN: 14584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18678

East Asian (EAS) AF: 0.00 AC: 0 AN: 27690

South Asian (SAS) AF: 0.00 AC: 0 AN: 57466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3730

European-Non Finnish (NFE) AF: 0.00000198 AC: 2 AN: 1010406

Other (OTH) AF: 0.00 AC: 0 AN: 50992

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151918 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74234

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67922

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.20
DANN	Benign	0.89
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.25
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.65	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.033
MutPred		0.29		Gain of sheet (P = 0.0266)
MVP		0.048
ClinPred		0.10	T
GERP RS		-0.84
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.6
Varity_R		0.026
gMVP		0.11
Mutation Taster		=98/2	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: rs2079317690; hg19: chr2-97482172;