chr2-96833166-GC-G

Variant names:

• chr2-96833166-GC-G
• rs34611972
• ENST00000465224.5:n.2200delC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000465224.5(CNNM3):​n.2200delC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 334,298 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: CNNM3 ENST00000465224.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

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]

LOC124907859 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465224.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM3	NM_017623.5	MANE Select	c.*554delC		3_prime_UTR	Exon 8 of 8	NP_060093.3
	CNNM3	NM_199078.3		c.*554delC		3_prime_UTR	Exon 7 of 7	NP_951060.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM3	ENST00000465224.5	TSL:1	n.2200delC		non_coding_transcript_exon	Exon 4 of 4
	CNNM3	ENST00000305510.4	TSL:1 MANE Select	c.*554delC		3_prime_UTR	Exon 8 of 8	ENSP00000305449.3
	CNNM3	ENST00000377060.7	TSL:2	c.*554delC		3_prime_UTR	Exon 7 of 7	ENSP00000366260.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000299 AC: 1 AN: 334298 Hom.: 0 Cov.: 5 AF XY: 0.00000561 AC XY: 1 AN XY: 178134

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 8208

American (AMR) AF: 0.00 AC: 0 AN: 19226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6718

East Asian (EAS) AF: 0.00 AC: 0 AN: 9018

South Asian (SAS) AF: 0.00 AC: 0 AN: 49524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1038

European-Non Finnish (NFE) AF: 0.00000462 AC: 1 AN: 216326

Other (OTH) AF: 0.00 AC: 0 AN: 14342

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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

Other links and lift over

dbSNP: rs34611972; hg19: chr2-97498903;