1-159171823-G-T

Position:

• chr1-159171823-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001127173.3(CADM3):​c.58G>T​(p.Ala20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,093,730 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: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CADM3 NM_001127173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26516044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM3	NM_001127173.3	c.58G>T	p.Ala20Ser	missense_variant	1/9	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5	c.58G>T	p.Ala20Ser	missense_variant	1/10		NP_067012.1
CADM3	NM_001346510.2	c.58G>T	p.Ala20Ser	missense_variant	1/9		NP_001333439.1
CADM3	XM_024448760.2	c.58G>T	p.Ala20Ser	missense_variant	1/12		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9	c.58G>T	p.Ala20Ser	missense_variant	1/9	1	NM_001127173.3	ENSP00000357107.4
CADM3	ENST00000368124.8	c.58G>T	p.Ala20Ser	missense_variant	1/10	1		ENSP00000357106.4
CADM3	ENST00000416746.1	c.58G>T	p.Ala20Ser	missense_variant	1/7	1		ENSP00000387802.1
AIM2	ENST00000695582.1	n.33+15988C>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1093730 Hom.: 0 Cov.: 31 AF XY: 0.00000386 AC XY: 2 AN XY: 517794

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: 0.00000216

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.58G>T (p.A20S) alteration is located in exon 1 (coding exon 1) of the CADM3 gene. This alteration results from a G to T substitution at nucleotide position 58, causing the alanine (A) at amino acid position 20 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	.;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.060	N;N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;T;T
Sift4G	Pathogenic	0.0	D;T;T
Polyphen		0.97	D;P;.
Vest4		0.23
MutPred		0.49		Gain of disorder (P = 0.0512);Gain of disorder (P = 0.0512);Gain of disorder (P = 0.0512);
MVP		0.44
MPC		0.93
ClinPred		0.74	D
GERP RS		3.7
Varity_R		0.090
gMVP		0.19

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: chr1-159141613;