10-99368605-C-T

Variant names:

• chr10-99368605-C-T
• rs17568778
• NM_020348.3:c.2176+3603C>T

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.2176+3603C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,137,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CNNM1 NM_020348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410
• Publications: 1 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 (BayesDel_noAF=-0.29).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM1	NM_020348.3	c.2176+3603C>T		intron_variant	Intron 6 of 10	ENST00000356713.5	NP_065081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM1	ENST00000356713.5	c.2176+3603C>T		intron_variant	Intron 6 of 10	1	NM_020348.3	ENSP00000349147.4
CNNM1	ENST00000488090.1	n.269C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
CNNM1	ENST00000696687.1	c.2177-13C>T		intron_variant	Intron 6 of 11			ENSP00000512809.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000743 AC: 1 AN: 134544 AF XY: 0.00

Gnomad AFR exome AF: 0.000155

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: 0.00000616 AC: 7 AN: 1137144 Hom.: 0 Cov.: 30 AF XY: 0.00000538 AC XY: 3 AN XY: 557886

African (AFR) AF: 0.0000410 AC: 1 AN: 24404

American (AMR) AF: 0.00 AC: 0 AN: 28264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15942

East Asian (EAS) AF: 0.00 AC: 0 AN: 12840

South Asian (SAS) AF: 0.00 AC: 0 AN: 76198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4402

European-Non Finnish (NFE) AF: 0.00000652 AC: 6 AN: 920494

Other (OTH) AF: 0.00 AC: 0 AN: 41522

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 686

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Benign	0.76
PhyloP100		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17568778; hg19: chr10-101128362;