1-159192042-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001127173.3(CADM3):c.195T>G(p.Pro65=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000687 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (0 hom.)
• Consequence: CADM3 NM_001127173.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-159192042-T-G is Benign according to our data. Variant chr1-159192042-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.034 with no splicing effect.
• BS2: High AC in GnomAd at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM3	NM_001127173.3	c.195T>G	p.Pro65=	synonymous_variant	2/9	ENST00000368125.9
CADM3	NM_021189.5	c.297T>G	p.Pro99=	synonymous_variant	3/10
CADM3	NM_001346510.2	c.195T>G	p.Pro65=	synonymous_variant	2/9
CADM3	XM_024448760.2	c.444T>G	p.Pro148=	synonymous_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM3	ENST00000368125.9	c.195T>G	p.Pro65=	synonymous_variant	2/9	1	NM_001127173.3	P2
CADM3	ENST00000368124.8	c.297T>G	p.Pro99=	synonymous_variant	3/10	1		A2
CADM3	ENST00000416746.1	c.195T>G	p.Pro65=	synonymous_variant	2/7	1

Frequencies

GnomAD3 genomes AF: 0.000499 AC: 76 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000488 AC: 122 AN: 250190 Hom.: 0 AF XY: 0.000458 AC XY: 62 AN XY: 135250

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.000901

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000707 AC: 1033 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.000721 AC XY: 524 AN XY: 727194

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.000874

Gnomad4 OTH exome AF: 0.000497

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37 AN XY: 74486

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000535 Hom.: 0

Bravo AF: 0.000434

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

CADM3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	11
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs140248716; hg19: chr1-159161832;