chr2-96817074-C-G

Variant names:

• chr2-96817074-C-G
• rs1331272597
• NM_017623.5:c.797C>G

Variant summary

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

The NM_017623.5(CNNM3):​c.797C>G​(p.Thr266Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000331 in 1,206,918 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: CNNM3 NM_017623.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18
• 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.797C>G	p.Thr266Ser	missense	Exon 1 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.797C>G	p.Thr266Ser	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.797C>G	p.Thr266Ser	missense	Exon 1 of 8	ENSP00000305449.3	Q8NE01-1
	CNNM3	ENST00000947263.1		c.797C>G	p.Thr266Ser	missense	Exon 1 of 8	ENSP00000617322.1
	CNNM3	ENST00000947265.1		c.797C>G	p.Thr266Ser	missense	Exon 1 of 8	ENSP00000617324.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000331 AC: 4 AN: 1206918 Hom.: 0 Cov.: 31 AF XY: 0.00000677 AC XY: 4 AN XY: 590918

African (AFR) AF: 0.00 AC: 0 AN: 23568

American (AMR) AF: 0.00 AC: 0 AN: 11716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17290

East Asian (EAS) AF: 0.00 AC: 0 AN: 26348

South Asian (SAS) AF: 0.0000189 AC: 1 AN: 52996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3846

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 993948

Other (OTH) AF: 0.0000205 AC: 1 AN: 48882

GnomAD4 genome Cov.: 32

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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.020	D
MutationAssessor	Benign	1.8	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.058	T
Polyphen		0.92	P
Vest4		0.27
MutPred		0.58		Gain of disorder (P = 0.0676)
MVP		0.21
ClinPred		0.88	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.52
Mutation Taster		=71/29	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: rs1331272597; hg19: chr2-97482811;