dbSNP rs1320149: CNNM3:p.Phe577Phe (chr2-96828140-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017623.5(CNNM3):c.1731T>C(p.Phe577Phe) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

13 publications found

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]

CNNM3 links:

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]

ANKRD23 links:

CNNM3-DT (HGNC:53592): (CNNM3 divergent transcript)

CNNM3-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNNM3	NM_017623.5 link	c.1731T>C	p.Phe577Phe	synonymous_variant	Exon 5 of 8	ENST00000305510.4	NP_060093.3	Q8NE01-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM3	ENST00000305510.4 link	c.1731T>C	p.Phe577Phe	synonymous_variant	Exon 5 of 8	1	NM_017623.5	ENSP00000305449.3		Q8NE01-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41243

AN:

151926

Hom.:

11658

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.134

AC:

33605

AN:

251364

AF XY:

0.122

show subpopulations

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 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.:

AF XY:

0.0980

AC XY:

71295

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.755

AC:

25252

AN:

33466

American (AMR)

AF:

0.0994

AC:

4447

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

3888

AN:

26134

East Asian (EAS)

AF:

0.141

AC:

5611

AN:

39698

South Asian (SAS)

AF:

0.0809

AC:

6980

AN:

86254

European-Finnish (FIN)

AF:

0.0710

AC:

3793

AN:

53400

Middle Eastern (MID)

AF:

0.197

AC:

1136

AN:

5768

European-Non Finnish (NFE)

AF:

0.0775

AC:

86161

AN:

1111818

Other (OTH)

AF:

0.145

AC:

8739

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

5877

11755

17632

23510

29387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3440

6880

10320

13760

17200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.272

AC:

41354

AN:

152044

Hom.:

11713

Cov.:

AF XY:

0.266

AC XY:

19781

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.725

AC:

30049

AN:

41428

American (AMR)

AF:

0.163

AC:

2496

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

511

AN:

3468

East Asian (EAS)

AF:

0.153

AC:

790

AN:

5168

South Asian (SAS)

AF:

0.0953

AC:

459

AN:

4816

European-Finnish (FIN)

AF:

0.0665

AC:

705

AN:

10604

Middle Eastern (MID)

AF:

0.223

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0834

AC:

5669

AN:

67960

Other (OTH)

AF:

0.249

AC:

526

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

934

1868

2801

3735

4669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.169

Hom.:

3695

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

(source)

DANN

Benign

0.61

PhyloP100

-1.0

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over