2-96835063-G-C

Variant names:

• chr2-96835063-G-C
• rs9948
• NM_017623.5:c.*2447G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017623.5(CNNM3):​c.*2447G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,116 control chromosomes in the GnomAD database, including 5,781 homozygotes. 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 0.20 (5781 hom., cov: 32)
• Consequence: CNNM3 NM_017623.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45

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]

ANKRD23 (HGNC:24470): (ankyrin repeat domain 23) This gene is a member of the muscle ankyrin repeat protein (MARP) family and encodes a protein with four tandem ankyrin-like repeats. The protein is localized to the nucleus, functioning as a transcriptional regulator. Expression of this protein is induced during recovery following starvation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM3	NM_017623.5	c.*2447G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000305510.4	NP_060093.3
CNNM3	NM_199078.3	c.*2447G>C		3_prime_UTR_variant	Exon 7 of 7		NP_951060.1
CNNM3	XM_011510957.4	c.2060-1881G>C		intron_variant	Intron 7 of 7		XP_011509259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM3	ENST00000305510.4	c.*2447G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_017623.5	ENSP00000305449.3
ANKRD23	ENST00000476975.5	n.442-1523C>G		intron_variant	Intron 5 of 7	5

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30122 AN: 151998 Hom.: 5759 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.198 AC: 30193 AN: 152116 Hom.: 5781 Cov.: 32 AF XY: 0.193 AC XY: 14325 AN XY: 74372

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0623

Gnomad4 SAS AF: 0.0488

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.191

Alfa AF: 0.0371 Hom.: 41

Bravo AF: 0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.21
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9948; hg19: chr2-97500800; COSMIC: COSV58412478;