rs751376142

Variant names:

• chr10-99329829-C-T
• rs751376142
• NM_020348.3:c.442C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-99329829-C-T
• chr10-99329829-C-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020348.3(CNNM1):​c.442C>T​(p.Pro148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000063 in 1,429,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: CNNM1 NM_020348.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.616
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049280524).
• BS2: High AC in GnomAdExome4 at 8 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.442C>T	p.Pro148Ser	missense	Exon 1 of 11	NP_065081.2	Q9NRU3-1
	CNNM1	NM_001345887.2		c.442C>T	p.Pro148Ser	missense	Exon 1 of 12	NP_001332816.1	A0A8Q3SIV9
	CNNM1	NM_001345889.2		c.442C>T	p.Pro148Ser	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.442C>T	p.Pro148Ser	missense	Exon 1 of 11	ENSP00000349147.4	Q9NRU3-1
	CNNM1	ENST00000696687.1		c.442C>T	p.Pro148Ser	missense	Exon 1 of 12	ENSP00000512809.1	A0A8Q3SIV9
	CNNM1	ENST00000914274.1		c.442C>T	p.Pro148Ser	missense	Exon 1 of 10	ENSP00000584333.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152126 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000832 AC: 3 AN: 36078 AF XY: 0.0000496

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: 0.000153

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000626 AC: 8 AN: 1277432 Hom.: 0 Cov.: 29 AF XY: 0.00000321 AC XY: 2 AN XY: 622790

African (AFR) AF: 0.00 AC: 0 AN: 25240

American (AMR) AF: 0.00 AC: 0 AN: 19160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19234

East Asian (EAS) AF: 0.00 AC: 0 AN: 28906

South Asian (SAS) AF: 0.0000159 AC: 1 AN: 63030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3882

European-Non Finnish (NFE) AF: 0.00000680 AC: 7 AN: 1029224

Other (OTH) AF: 0.00 AC: 0 AN: 52902

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000105 AC: 1

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	0.17
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.62
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	0.87	N
REVEL	Benign	0.17
Sift	Benign	0.33	T
Sift4G	Benign	0.75	T
Polyphen		0.033	B
Vest4		0.037
MutPred		0.12		Gain of phosphorylation at P148 (P = 0.0502)
MVP		0.10
ClinPred		0.035	T
GERP RS		2.9
PromoterAI		-0.054	Neutral
Varity_R		0.084
gMVP		0.38
Mutation Taster		=99/1	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: rs751376142; hg19: chr10-101089586;