chr2-96816680-T-C

Variant names:

• chr2-96816680-T-C
• rs905088464
• NM_017623.5:c.403T>C

Variant summary

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

The NM_017623.5(CNNM3):​c.403T>C​(p.Trp135Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,022,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CNNM3 NM_017623.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.193
• 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.

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.403T>C	p.Trp135Arg	missense	Exon 1 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.403T>C	p.Trp135Arg	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.403T>C	p.Trp135Arg	missense	Exon 1 of 8	ENSP00000305449.3	Q8NE01-1
	CNNM3	ENST00000947263.1		c.403T>C	p.Trp135Arg	missense	Exon 1 of 8	ENSP00000617322.1
	CNNM3	ENST00000947265.1		c.403T>C	p.Trp135Arg	missense	Exon 1 of 8	ENSP00000617324.1

Frequencies

GnomAD3 genomes AF: 0.000367 AC: 54 AN: 147088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00132

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 15 AN: 875410 Hom.: 0 Cov.: 30 AF XY: 0.0000122 AC XY: 5 AN XY: 408454

African (AFR) AF: 0.000784 AC: 13 AN: 16572

American (AMR) AF: 0.000409 AC: 1 AN: 2444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6256

East Asian (EAS) AF: 0.00 AC: 0 AN: 5442

South Asian (SAS) AF: 0.00 AC: 0 AN: 17706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1832

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 790258

Other (OTH) AF: 0.0000335 AC: 1 AN: 29844

GnomAD4 genome AF: 0.000367 AC: 54 AN: 147088 Hom.: 0 Cov.: 32 AF XY: 0.000307 AC XY: 22 AN XY: 71550

African (AFR) AF: 0.00132 AC: 54 AN: 40870

American (AMR) AF: 0.00 AC: 0 AN: 14822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66086

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000495

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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.38	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.19
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-8.4	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.66	P
Vest4		0.51
MutPred		0.63		Loss of catalytic residue at W135 (P = 0.0016)
MVP		0.27
ClinPred		0.45	T
GERP RS		1.4
PromoterAI		-0.054	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
Varity_R		0.54
gMVP		0.70
Mutation Taster		=67/33	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: rs905088464; hg19: chr2-97482417;