chr2-96816569-C-T

Variant summary

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

The NM_017623.5(CNNM3):​c.292C>T​(p.Arg98Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,303,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CNNM3
NM_017623.5 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101
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]

Genome browser will be placed here

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=0.13868105).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNNM3NM_017623.5 linkc.292C>T p.Arg98Cys missense_variant Exon 1 of 8 ENST00000305510.4 NP_060093.3 Q8NE01-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNNM3ENST00000305510.4 linkc.292C>T p.Arg98Cys missense_variant Exon 1 of 8 1 NM_017623.5 ENSP00000305449.3 Q8NE01-1
CNNM3ENST00000377060.7 linkc.292C>T p.Arg98Cys missense_variant Exon 1 of 7 2 ENSP00000366260.3 Q8NE01-2

Frequencies

GnomAD3 genomes
AF:
0.00000663
AC:
1
AN:
150904
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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
GnomAD3 exomes
AF:
0.000269
AC:
1
AN:
3716
Hom.:
0
AF XY:
0.000414
AC XY:
1
AN XY:
2414
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 SAS exome
AF:
0.00207
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000113
AC:
13
AN:
1152900
Hom.:
0
Cov.:
31
AF XY:
0.0000143
AC XY:
8
AN XY:
559522
show subpopulations
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:
0.0000249
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000114
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
AF:
0.00000663
AC:
1
AN:
150904
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73690
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.292C>T (p.R98C) alteration is located in exon 1 (coding exon 1) of the CNNM3 gene. This alteration results from a C to T substitution at nucleotide position 292, causing the arginine (R) at amino acid position 98 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Uncertain
0.094
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
.;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.67
T;T
M_CAP
Pathogenic
0.99
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
0.81
L;L
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.73
N;N
REVEL
Benign
0.24
Sift
Uncertain
0.018
D;D
Sift4G
Uncertain
0.059
T;T
Polyphen
0.98
D;D
Vest4
0.28
MutPred
0.42
Loss of MoRF binding (P = 0.0127);Loss of MoRF binding (P = 0.0127);
MVP
0.52
ClinPred
0.20
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.23
gMVP
0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1265426274; hg19: chr2-97482306; API