dbSNP rs373318478: CNNM3:p.Arg10Arg (chr2-96816305-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_017623.5(CNNM3):c.28C>A(p.Arg10Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000544 in 1,287,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

CNNM3
NM_017623.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.577

Publications

2 publications found

Variant links:

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 links:

CNNM3-DT (HGNC:53592): (CNNM3 divergent transcript)

CNNM3-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.28C>A	p.Arg10Arg	synonymous	Exon 1 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 7	NP_951060.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CNNM3	ENST00000305510.4	TSL:1 MANE Select	c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 8	ENSP00000305449.3
CNNM3	ENST00000947263.1		c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 8	ENSP00000617322.1
CNNM3	ENST00000947265.1		c.28C>A	p.Arg10Arg	synonymous	Exon 1 of 8	ENSP00000617324.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151906

Hom.:

Cov.:

show subpopulations

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:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000519

AC:

AN:

19272

AF XY:

0.0000907

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000440

AC:

AN:

1135668

Hom.:

Cov.:

AF XY:

0.00000183

AC XY:

AN XY:

545314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23558

American (AMR)

AF:

0.00

AC:

AN:

10614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14972

East Asian (EAS)

AF:

0.00

AC:

AN:

27330

South Asian (SAS)

AF:

0.000149

AC:

AN:

33666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3046

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

951328

Other (OTH)

AF:

0.00

AC:

AN:

45496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41514

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67902

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.58

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.64

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.64

Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over