19-498524-A-T

Variant names:

• chr19-498524-A-T
• rs2302217
• NM_130760.3:c.366A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_130760.3(MADCAM1):​c.366A>T​(p.Pro122Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MADCAM1 NM_130760.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.48
• Publications: 19 publications found

Genes affected

MADCAM1 (HGNC:6765): (mucosal vascular addressin cell adhesion molecule 1) The protein encoded by this gene is an endothelial cell adhesion molecule that interacts preferentially with the leukocyte beta7 integrin LPAM-1 (alpha4beta7), L-selectin, and VLA-4 (alpha4beta1) on myeloid cells to direct leukocytes into mucosal and inflamed tissues. It is a member of the immunoglobulin family and is similar to ICAM1 and VCAM1. At least seven alternatively spliced transcripts encoding different protein isoforms have been found for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

MADCAM1-AS1 (HGNC:55315): (MADCAM1 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_130760.3. 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
	MADCAM1	NM_130760.3	MANE Select	c.366A>T	p.Pro122Pro	synonymous	Exon 3 of 5	NP_570116.2	Q13477-1
	MADCAM1	NM_130762.3		c.366A>T	p.Pro122Pro	synonymous	Exon 3 of 4	NP_570118.1	Q13477-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MADCAM1	ENST00000215637.8	TSL:1 MANE Select	c.366A>T	p.Pro122Pro	synonymous	Exon 3 of 5	ENSP00000215637.2	Q13477-1
	MADCAM1	ENST00000346144.8	TSL:1	c.366A>T	p.Pro122Pro	synonymous	Exon 3 of 4	ENSP00000304247.2	Q13477-3
	MADCAM1	ENST00000382683.8	TSL:1	c.81A>T	p.Pro27Pro	synonymous	Exon 2 of 3	ENSP00000372130.4	Q13477-4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1311700 Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0 AN XY: 641094

African (AFR) AF: 0.00 AC: 0 AN: 26274

American (AMR) AF: 0.00 AC: 0 AN: 21578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18616

East Asian (EAS) AF: 0.00 AC: 0 AN: 32306

South Asian (SAS) AF: 0.00 AC: 0 AN: 61792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5194

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1044694

Other (OTH) AF: 0.00 AC: 0 AN: 53806

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		-6.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.48		Position offset: 5

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

Other links and lift over

dbSNP: rs2302217; hg19: chr19-498524;