chr1-159193467-C-A

Variant names:

• chr1-159193467-C-A
• NM_001127173.3:c.427C>A

Variant summary

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

The NM_001127173.3(CADM3):​c.427C>A​(p.Arg143Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,718 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: 6.9e-7 (0 hom.)
• Consequence: CADM3 NM_001127173.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576

Genes affected

CADM3 (HGNC:17601): (cell adhesion molecule 3) The protein encoded by this gene is a calcium-independent cell-cell adhesion protein that can form homodimers or heterodimers with other nectin proteins. The encoded protein has both homophilic and heterophilic cell-cell adhesion activity. This gene is reported to be a tumor suppressor gene. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM3	NM_001127173.3	c.427C>A	p.Arg143Arg	synonymous_variant	Exon 4 of 9	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5	c.529C>A	p.Arg177Arg	synonymous_variant	Exon 5 of 10		NP_067012.1
CADM3	NM_001346510.2	c.427C>A	p.Arg143Arg	synonymous_variant	Exon 4 of 9		NP_001333439.1
CADM3	XM_024448760.2	c.676C>A	p.Arg226Arg	synonymous_variant	Exon 7 of 12		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9	c.427C>A	p.Arg143Arg	synonymous_variant	Exon 4 of 9	1	NM_001127173.3	ENSP00000357107.4
CADM3	ENST00000368124.8	c.529C>A	p.Arg177Arg	synonymous_variant	Exon 5 of 10	1		ENSP00000357106.4
CADM3	ENST00000416746.1	c.427C>A	p.Arg143Arg	synonymous_variant	Exon 4 of 7	1		ENSP00000387802.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459718 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725766

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 2
DS_AL_spliceai		0.30		Position offset: -44

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: chr1-159163257;