rs1320149

chr2-96828140-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017623.5(CNNM3):c.1731T>C(p.Phe577=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,686 control chromosomes in the GnomAD database, including 27,264 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 0.27 (11713 hom., cov: 32)
  • Exomes 𝑓: 0.10 (15551 hom.)
• Consequence: CNNM3 NM_017623.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNNM3	NM_017623.5	c.1731T>C	p.Phe577=	synonymous_variant	5/8	ENST00000305510.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM3	ENST00000305510.4	c.1731T>C	p.Phe577=	synonymous_variant	5/8	1	NM_017623.5	P1
CNNM3	ENST00000465224.5	n.587T>C		non_coding_transcript_exon_variant	3/4	1
CNNM3	ENST00000377060.7	c.1587T>C	p.Phe529=	synonymous_variant	4/7	2
ANKRD23	ENST00000476975.5	n.799-3281A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41243 AN: 151926 Hom.: 11658 Cov.: 32

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.247

GnomAD3 exomes AF: 0.134 AC: 33605 AN: 251364 Hom.: 5684 AF XY: 0.122 AC XY: 16550 AN XY: 135856

Gnomad AFR exome AF: 0.745

Gnomad AMR exome AF: 0.0918

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.149

Gnomad SAS exome AF: 0.0792

Gnomad FIN exome AF: 0.0718

Gnomad NFE exome AF: 0.0824

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.0999 AC: 146007 AN: 1461642 Hom.: 15551 Cov.: 32 AF XY: 0.0980 AC XY: 71295 AN XY: 727134

Gnomad4 AFR exome AF: 0.755

Gnomad4 AMR exome AF: 0.0994

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.0809

Gnomad4 FIN exome AF: 0.0710

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.272 AC: 41354 AN: 152044 Hom.: 11713 Cov.: 32 AF XY: 0.266 AC XY: 19781 AN XY: 74336

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0953

Gnomad4 FIN AF: 0.0665

Gnomad4 NFE AF: 0.0834

Gnomad4 OTH AF: 0.249

Alfa AF: 0.162 Hom.: 3184

Bravo AF: 0.299

Asia WGS AF: 0.217 AC: 751 AN: 3478

EpiCase AF: 0.0946

EpiControl AF: 0.0883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	2.5
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1320149; hg19: chr2-97493877; COSMIC: COSV59709294; COSMIC: COSV59709294;