NM_001127173.3:c.56G>A

Variant names:

• chr1-159171821-G-A
• NM_001127173.3:c.56G>A

Variant summary

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

The NM_001127173.3(CADM3):​c.56G>A​(p.Trp19*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,094,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: CADM3 NM_001127173.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

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]

AIM2 (HGNC:357): (absent in melanoma 2) AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

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.56G>A	p.Trp19*	stop_gained	Exon 1 of 9	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5	c.56G>A	p.Trp19*	stop_gained	Exon 1 of 10		NP_067012.1
CADM3	NM_001346510.2	c.56G>A	p.Trp19*	stop_gained	Exon 1 of 9		NP_001333439.1
CADM3	XM_024448760.2	c.56G>A	p.Trp19*	stop_gained	Exon 1 of 12		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9	c.56G>A	p.Trp19*	stop_gained	Exon 1 of 9	1	NM_001127173.3	ENSP00000357107.4
CADM3	ENST00000368124.8	c.56G>A	p.Trp19*	stop_gained	Exon 1 of 10	1		ENSP00000357106.4
CADM3	ENST00000416746.1	c.56G>A	p.Trp19*	stop_gained	Exon 1 of 7	1		ENSP00000387802.1
AIM2	ENST00000695582.1	n.33+15990C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1094378 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 518158

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: 0.00

Gnomad4 OTH exome AF: 0.0000226

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	40
DANN	Uncertain	0.99
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.66	D
Vest4		0.15
GERP RS		3.7

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: chr1-159141611;