rs776871459

Variant names:

• chr10-99330221-G-C
• rs776871459
• NM_020348.3:c.834G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-99330221-G-C
• chr10-99330221-G-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020348.3(CNNM1):​c.834G>C​(p.Arg278Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,521,064 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CNNM1 NM_020348.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.783
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1480433).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM1	NM_020348.3	MANE Select	c.834G>C	p.Arg278Ser	missense	Exon 1 of 11	NP_065081.2	Q9NRU3-1
	CNNM1	NM_001345887.2		c.834G>C	p.Arg278Ser	missense	Exon 1 of 12	NP_001332816.1	A0A8Q3SIV9
	CNNM1	NM_001345889.2		c.834G>C	p.Arg278Ser	missense	Exon 1 of 11	NP_001332818.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM1	ENST00000356713.5	TSL:1 MANE Select	c.834G>C	p.Arg278Ser	missense	Exon 1 of 11	ENSP00000349147.4	Q9NRU3-1
	CNNM1	ENST00000696687.1		c.834G>C	p.Arg278Ser	missense	Exon 1 of 12	ENSP00000512809.1	A0A8Q3SIV9
	CNNM1	ENST00000914274.1		c.834G>C	p.Arg278Ser	missense	Exon 1 of 10	ENSP00000584333.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000168 AC: 23 AN: 1368834 Hom.: 0 Cov.: 29 AF XY: 0.0000208 AC XY: 14 AN XY: 672690

African (AFR) AF: 0.00 AC: 0 AN: 31274

American (AMR) AF: 0.00 AC: 0 AN: 32896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22510

East Asian (EAS) AF: 0.00 AC: 0 AN: 36036

South Asian (SAS) AF: 0.00 AC: 0 AN: 73344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 0.0000196 AC: 21 AN: 1069844

Other (OTH) AF: 0.0000352 AC: 2 AN: 56792

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.78
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Benign	0.12	T
Sift4G	Benign	0.10	T
Polyphen		0.0090	B
Vest4		0.076
MutPred		0.53		Gain of glycosylation at R278 (P = 0.0087)
MVP		0.12
ClinPred		0.093	T
GERP RS		2.2
Varity_R		0.12
gMVP		0.40
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs776871459; hg19: chr10-101089978;