NM_001127173.3:c.427C>A

Variant names:

• chr1-159193467-C-A
• rs1021719284
• NM_001127173.3:c.427C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

CADM3-AS1 (HGNC:40812): (CADM3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127173.3. 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
	CADM3	NM_001127173.3	MANE Select	c.427C>A	p.Arg143Arg	synonymous	Exon 4 of 9	NP_001120645.1	Q8N126-1
	CADM3	NM_021189.5		c.529C>A	p.Arg177Arg	synonymous	Exon 5 of 10	NP_067012.1	Q8N126-2
	CADM3	NM_001346510.2		c.427C>A	p.Arg143Arg	synonymous	Exon 4 of 9	NP_001333439.1	Q8N126-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM3	ENST00000368125.9	TSL:1 MANE Select	c.427C>A	p.Arg143Arg	synonymous	Exon 4 of 9	ENSP00000357107.4	Q8N126-1
	CADM3	ENST00000368124.8	TSL:1	c.529C>A	p.Arg177Arg	synonymous	Exon 5 of 10	ENSP00000357106.4	Q8N126-2
	CADM3	ENST00000416746.1	TSL:1	c.427C>A	p.Arg143Arg	synonymous	Exon 4 of 7	ENSP00000387802.1	A0A0C4DG09

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

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110378

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1021719284; hg19: chr1-159163257;