10-99329490-C-G

Variant names:

• chr10-99329490-C-G
• NM_020348.3:c.103C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020348.3(CNNM1):​c.103C>G​(p.Pro35Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,344,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. P35S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: CNNM1 NM_020348.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1045492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM1	NM_020348.3	c.103C>G	p.Pro35Ala	missense_variant	Exon 1 of 11	ENST00000356713.5	NP_065081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM1	ENST00000356713.5	c.103C>G	p.Pro35Ala	missense_variant	Exon 1 of 11	1	NM_020348.3	ENSP00000349147.4
CNNM1	ENST00000696687.1	c.103C>G	p.Pro35Ala	missense_variant	Exon 1 of 12			ENSP00000512809.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1344352 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 663472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.47e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.21
Sift	Benign	0.12	T
Sift4G	Benign	0.74	T
Polyphen		0.048	B
Vest4		0.16
MutPred		0.23		Loss of glycosylation at P35 (P = 0.0091);
MVP		0.27
ClinPred		0.28	T
GERP RS		3.8
Varity_R		0.093
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-101089247;