Variant 10-99330053-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020348.3(CNNM1):c.666G>A(p.Ala222Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,512,102 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 58 hom. )

Consequence

CNNM1
NM_020348.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.193

Variant links:

Genes affected

CNNM1 (HGNC:102): (cyclin and CBS domain divalent metal cation transport mediator 1) This gene encodes a member of the ancient conserved domain protein family. The encoded protein may bind copper. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

CNNM1 links:

CNNM1 (HGNC:):

CNNM1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 10-99330053-G-A is Benign according to our data. Variant chr10-99330053-G-A is described in ClinVar as [Benign]. Clinvar id is 1181501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.193 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0046 (701/152318) while in subpopulation AMR AF= 0.0261 (400/15308). AF 95% confidence interval is 0.024. There are 17 homozygotes in gnomad4. There are 365 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 701 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM1	NM_020348.3 linkuse as main transcript	c.666G>A	p.Ala222Ala	synonymous_variant	1/11	ENST00000356713.5	NP_065081.2	Q9NRU3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM1	ENST00000356713.5 linkuse as main transcript	c.666G>A	p.Ala222Ala	synonymous_variant	1/11	1	NM_020348.3	ENSP00000349147.4		Q9NRU3-1
CNNM1	ENST00000696687.1 linkuse as main transcript	c.666G>A	p.Ala222Ala	synonymous_variant	1/12			ENSP00000512809.1		A0A8Q3SIV9

Frequencies

GnomAD3 genomes

AF:

0.00452

AC:

688

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0252

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0252

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.0132

AC:

1424

AN:

107960

Hom.:

AF XY:

0.00990

AC XY:

605

AN XY:

61106

show subpopulations

Gnomad AFR exome

AF:

0.00151

Gnomad AMR exome

AF:

0.0528

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.0254

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.000369

Gnomad NFE exome

AF:

0.000681

Gnomad OTH exome

AF:

0.00920

GnomAD4 exome

AF:

0.00250

AC:

3401

AN:

1359784

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

1562

AN XY:

671720

show subpopulations

Gnomad4 AFR exome

AF:

0.000752

Gnomad4 AMR exome

AF:

0.0485

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.0279

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.000238

Gnomad4 NFE exome

AF:

0.000355

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00460

AC:

701

AN:

152318

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

365

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.0261

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0253

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.00696

Asia WGS

AF:

0.00984

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over