Genetic Variant CNNM3:p.Ser114Leu (chr2-96816618-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017623.5(CNNM3):c.341C>T(p.Ser114Leu) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.576

Publications

0 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17103142).

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.341C>T	p.Ser114Leu	missense	Exon 1 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.341C>T	p.Ser114Leu	missense	Exon 1 of 7	NP_951060.1	Q8NE01-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNNM3	ENST00000305510.4	TSL:1 MANE Select	c.341C>T	p.Ser114Leu	missense	Exon 1 of 8	ENSP00000305449.3	Q8NE01-1
CNNM3	ENST00000947263.1		c.341C>T	p.Ser114Leu	missense	Exon 1 of 8	ENSP00000617322.1
CNNM3	ENST00000947265.1		c.341C>T	p.Ser114Leu	missense	Exon 1 of 8	ENSP00000617324.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1024214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

482910

African (AFR)

AF:

0.00

AC:

AN:

20756

American (AMR)

AF:

0.00

AC:

AN:

6490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11708

East Asian (EAS)

AF:

0.00

AC:

AN:

20998

South Asian (SAS)

AF:

0.00

AC:

AN:

19024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2588

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

883962

Other (OTH)

AF:

0.00

AC:

AN:

39346

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.17

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

0.90

PhyloP100

0.58

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.0

REVEL

Benign

0.28

Sift

Benign

0.13

Sift4G

Benign

0.54

Polyphen

0.071

Vest4

0.12

MutPred

0.33

Loss of loop (P = 0.0112)

MVP

0.25

ClinPred

0.14

GERP RS

2.3

PromoterAI

-0.099

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.092

gMVP

0.51

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over