16-68645239-C-T

Variant names:

• chr16-68645239-C-T
• rs537339409
• ENST00000429102.6:c.-141C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000429102.6(CDH3):​c.-141C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000459 in 653,522 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: 33)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: CDH3 ENST00000429102.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 0 publications found

Genes affected

CDH3 (HGNC:1762): (cadherin 3) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS). [provided by RefSeq, Nov 2015]

CDH3-AS1 (HGNC:56084): (CDH3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429102.6. 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
	CDH3-AS1	NR_186394.1		n.724G>A		non_coding_transcript_exon	Exon 2 of 2
	CDH3	NM_001793.6	MANE Select	c.-141C>T		upstream_gene	N/A	NP_001784.2
	CDH3	NM_001317195.3		c.-141C>T		upstream_gene	N/A	NP_001304124.1	P22223-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH3	ENST00000429102.6	TSL:1	c.-141C>T		5_prime_UTR	Exon 1 of 16	ENSP00000398485.2	P22223-2
	CDH3-AS1	ENST00000562172.2	TSL:3	n.691G>A		non_coding_transcript_exon	Exon 2 of 2
	CDH3	ENST00000565453.1	TSL:4	n.453C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000459 AC: 3 AN: 653522 Hom.: 0 Cov.: 9 AF XY: 0.00000577 AC XY: 2 AN XY: 346768

African (AFR) AF: 0.00 AC: 0 AN: 17648

American (AMR) AF: 0.00 AC: 0 AN: 34616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20128

East Asian (EAS) AF: 0.00 AC: 0 AN: 32518

South Asian (SAS) AF: 0.00 AC: 0 AN: 63826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3914

European-Non Finnish (NFE) AF: 0.00000728 AC: 3 AN: 411832

Other (OTH) AF: 0.00 AC: 0 AN: 33754

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.95
PhyloP100		-0.011
PromoterAI		-0.0049	Neutral

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

Other links and lift over

dbSNP: rs537339409; hg19: chr16-68679142;