dbSNP rs1024761477: CNNM3:p.Ala7Glu (chr2-96816297-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017623.5(CNNM3):c.20C>A(p.Ala7Glu) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNNM3
NM_017623.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0140

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:

ENSG00000289135 (HGNC:):

ENSG00000289135 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2439054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM3	NM_017623.5 link	c.20C>A	p.Ala7Glu	missense_variant	Exon 1 of 8	ENST00000305510.4	NP_060093.3	Q8NE01-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNNM3	ENST00000305510.4 link	c.20C>A	p.Ala7Glu	missense_variant	Exon 1 of 8	1	NM_017623.5	ENSP00000305449.3	Q8NE01-1
CNNM3	ENST00000377060.7 link	c.20C>A	p.Ala7Glu	missense_variant	Exon 1 of 7	2		ENSP00000366260.3	Q8NE01-2
ENSG00000289135	ENST00000690930.2 link	n.-219G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1138596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

546808

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.36

T;T

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.81

L;L

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.30

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.40

B;B

Vest4

0.15

MutPred

0.43

Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);

MVP

0.061

ClinPred

0.19

GERP RS

-1.6

Varity_R

0.11

gMVP

0.35

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over