Variant 4-120066704-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002358.4(MAD2L1):c.31A>G(p.Ile11Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000689 in 1,452,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

MAD2L1
NM_002358.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.02

Variant links:

Genes affected

MAD2L1 (HGNC:6763): (mitotic arrest deficient 2 like 1) MAD2L1 is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. MAD2L1 is related to the MAD2L2 gene located on chromosome 1. A MAD2 pseudogene has been mapped to chromosome 14. [provided by RefSeq, Jul 2008]

MAD2L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3070618).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAD2L1	NM_002358.4 linkuse as main transcript	c.31A>G	p.Ile11Val	missense_variant	1/5	ENST00000296509.11	NP_002349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAD2L1	ENST00000296509.11 linkuse as main transcript	c.31A>G	p.Ile11Val	missense_variant	1/5	1	NM_002358.4	ENSP00000296509	P1	Q13257-1
MAD2L1	ENST00000333047.9 linkuse as main transcript	c.31A>G	p.Ile11Val	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000332295		Q13257-2
MAD2L1	ENST00000511295.1 linkuse as main transcript	n.118A>G		non_coding_transcript_exon_variant	1/2	2
MAD2L1	ENST00000504707.1 linkuse as main transcript	c.31A>G	p.Ile11Val	missense_variant, NMD_transcript_variant	1/3	2		ENSP00000425702

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000365

AC:

AN:

246336

Hom.:

AF XY:

0.0000525

AC XY:

AN XY:

133426

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000492

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000689

AC:

AN:

1452020

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

720750

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.31A>G (p.I11V) alteration is located in exon 1 (coding exon 1) of the MAD2L1 gene. This alteration results from a A to G substitution at nucleotide position 31, causing the isoleucine (I) at amino acid position 11 to be replaced by a valine (V). 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

0.28

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.31

MetaSVM

Uncertain

-0.018

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.92

REVEL

Uncertain

0.44

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0060

Polyphen

0.68

Vest4

0.38

MutPred

0.68

Gain of glycosylation at S16 (P = 0.0426);

MVP

0.68

MPC

0.52

ClinPred

0.65

GERP RS

5.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.74

gMVP

0.71

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over