10-99330344-G-C

Position:

• chr10-99330344-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020348.3(CNNM1):​c.957G>C​(p.Glu319Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNNM1 NM_020348.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.00

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056898206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM1	NM_020348.3	c.957G>C	p.Glu319Asp	missense_variant	1/11	ENST00000356713.5	NP_065081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM1	ENST00000356713.5	c.957G>C	p.Glu319Asp	missense_variant	1/11	1	NM_020348.3	ENSP00000349147.4
CNNM1	ENST00000696687.1	c.957G>C	p.Glu319Asp	missense_variant	1/12			ENSP00000512809.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Breast ductal adenocarcinoma Uncertain:1

Uncertain significance, no assertion criteria provided

research

Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.

Jul 20, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	5.8
DANN	Benign	0.91
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.40	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.16
Sift	Benign	0.32	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.078
MutPred		0.44		Loss of phosphorylation at Y316 (P = 0.079);
MVP		0.11
ClinPred		0.14	T
GERP RS		-0.53
Varity_R		0.061
gMVP		0.28

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

Other links and lift over

dbSNP: rs869025226; hg19: chr10-101090101;