NM_130760.3:c.348C>G

Variant names:

• chr19-498506-C-G
• rs752197327
• NM_130760.3:c.348C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130760.3(MADCAM1):​c.348C>G​(p.Asp116Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,465,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: MADCAM1 NM_130760.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.73
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14908019).

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.348C>G	p.Asp116Glu	missense	Exon 3 of 5	NP_570116.2	Q13477-1
	MADCAM1	NM_130762.3		c.348C>G	p.Asp116Glu	missense	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.348C>G	p.Asp116Glu	missense	Exon 3 of 5	ENSP00000215637.2	Q13477-1
	MADCAM1	ENST00000346144.8	TSL:1	c.348C>G	p.Asp116Glu	missense	Exon 3 of 4	ENSP00000304247.2	Q13477-3
	MADCAM1	ENST00000382683.8	TSL:1	c.63C>G	p.Asp21Glu	missense	Exon 2 of 3	ENSP00000372130.4	Q13477-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000772 AC: 1 AN: 129464 AF XY: 0.0000142

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000149

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1313022 Hom.: 0 Cov.: 30 AF XY: 0.00000156 AC XY: 1 AN XY: 641552

African (AFR) AF: 0.00 AC: 0 AN: 26404

American (AMR) AF: 0.00 AC: 0 AN: 21760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18630

East Asian (EAS) AF: 0.00 AC: 0 AN: 32610

South Asian (SAS) AF: 0.00 AC: 0 AN: 61956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5202

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1045402

Other (OTH) AF: 0.00 AC: 0 AN: 53906

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000843 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.23	T
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.15
MutPred		0.63		Loss of sheet (P = 0.0817)
MVP		0.20
MPC		0.32
ClinPred		0.29	T
GERP RS		3.1
Varity_R		0.067
gMVP		0.22
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs752197327; hg19: chr19-498506;