dbSNP rs781664354: CNNM1:p.Gly311Asp (chr10-99330319-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020348.3(CNNM1):c.932G>A(p.Gly311Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G311A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CNNM1
NM_020348.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.987

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.067967).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020348.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNNM1	NM_020348.3	MANE Select	c.932G>A	p.Gly311Asp	missense	Exon 1 of 11	NP_065081.2	Q9NRU3-1
CNNM1	NM_001345887.2		c.932G>A	p.Gly311Asp	missense	Exon 1 of 12	NP_001332816.1	A0A8Q3SIV9
CNNM1	NM_001345889.2		c.932G>A	p.Gly311Asp	missense	Exon 1 of 11	NP_001332818.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNNM1	ENST00000356713.5	TSL:1 MANE Select	c.932G>A	p.Gly311Asp	missense	Exon 1 of 11	ENSP00000349147.4	Q9NRU3-1
CNNM1	ENST00000696687.1		c.932G>A	p.Gly311Asp	missense	Exon 1 of 12	ENSP00000512809.1	A0A8Q3SIV9
CNNM1	ENST00000914274.1		c.932G>A	p.Gly311Asp	missense	Exon 1 of 10	ENSP00000584333.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

210254

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442742

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

715276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33144

American (AMR)

AF:

0.0000235

AC:

AN:

42550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25580

East Asian (EAS)

AF:

0.00

AC:

AN:

38932

South Asian (SAS)

AF:

0.0000241

AC:

AN:

83016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103518

Other (OTH)

AF:

0.00

AC:

AN:

59540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.49

CADD

Benign

1.2

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.30

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.54

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.97

PhyloP100

-0.99

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.85

REVEL

Benign

0.18

Sift

Benign

0.11

Sift4G

Benign

0.074

Polyphen

0.0

Vest4

0.079

MutPred

0.39

Gain of loop (P = 0.1081)

MVP

0.15

ClinPred

0.027

GERP RS

-4.3

Varity_R

0.066

gMVP

0.43

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over