2-96817076-C-A

Variant names:

• chr2-96817076-C-A
• rs1015625758
• NM_017623.5:c.799C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017623.5(CNNM3):​c.799C>A​(p.Leu267Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM3	NM_017623.5	c.799C>A	p.Leu267Met	missense_variant	Exon 1 of 8	ENST00000305510.4	NP_060093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM3	ENST00000305510.4	c.799C>A	p.Leu267Met	missense_variant	Exon 1 of 8	1	NM_017623.5	ENSP00000305449.3
CNNM3	ENST00000377060.7	c.799C>A	p.Leu267Met	missense_variant	Exon 1 of 7	2		ENSP00000366260.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1201430 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 587556

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.63	T;T
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.037	D;D
Polyphen		0.89	P;P
Vest4		0.23
MutPred		0.51		Gain of catalytic residue at V263 (P = 0.0792);Gain of catalytic residue at V263 (P = 0.0792);
MVP		0.12
ClinPred		0.33	T
GERP RS		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.38

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

Other links and lift over

dbSNP: rs1015625758; hg19: chr2-97482813;