dbSNP rs376416942: MADCAM1:p.Ala161Thr (chr19-498639-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130760.3(MADCAM1):c.481G>A(p.Ala161Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,315,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 0.0000038 ( 0 hom. )

Consequence

MADCAM1
NM_130760.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.223

Variant links:

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 links:

MADCAM1-AS1 (HGNC:55315): (MADCAM1 antisense RNA 1)

MADCAM1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10762069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MADCAM1	NM_130760.3 link	c.481G>A	p.Ala161Thr	missense_variant	Exon 3 of 5	ENST00000215637.8	NP_570116.2	Q13477-1
MADCAM1	NM_130762.3 link	c.481G>A	p.Ala161Thr	missense_variant	Exon 3 of 4		NP_570118.1	Q13477-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MADCAM1	ENST00000215637.8 link	c.481G>A	p.Ala161Thr	missense_variant	Exon 3 of 5	1	NM_130760.3	ENSP00000215637.2		Q13477-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000943

AC:

AN:

106058

Hom.:

AF XY:

0.0000175

AC XY:

AN XY:

57278

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000380

AC:

AN:

1315004

Hom.:

Cov.:

AF XY:

0.00000467

AC XY:

AN XY:

642024

show subpopulations

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:

0.00000477

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000844

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T;T;T;.;T;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.068

LIST_S2

Uncertain

0.86

D;D;D;D;D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;.;.;.;L;L;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.88

.;.;.;.;N;N;N;.

REVEL

Benign

0.11

Sift

Benign

0.20

.;.;.;.;T;T;D;.

Sift4G

Benign

0.12

T;T;T;T;T;T;D;T

Polyphen

0.88

.;.;.;.;.;P;.;.

Vest4

0.069

MutPred

0.60

Gain of glycosylation at A161 (P = 0.0236);Gain of glycosylation at A161 (P = 0.0236);Gain of glycosylation at A161 (P = 0.0236);Gain of glycosylation at A161 (P = 0.0236);Gain of glycosylation at A161 (P = 0.0236);Gain of glycosylation at A161 (P = 0.0236);.;Gain of glycosylation at A161 (P = 0.0236);

MVP

0.12

MPC

0.65

ClinPred

0.16

GERP RS

3.1

Varity_R

0.28

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over