Variant 4-120060168-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002358.4(MAD2L1):c.568A>G(p.Ile190Val) variant causes a missense change. The variant allele was found at a frequency of 0.00543 in 1,611,508 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 42 hom. )

Consequence

MAD2L1
NM_002358.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.82

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01329425).

BP6

Variant 4-120060168-T-C is Benign according to our data. Variant chr4-120060168-T-C is described in ClinVar as [Benign]. Clinvar id is 782943.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 551 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAD2L1	NM_002358.4 linkuse as main transcript	c.568A>G	p.Ile190Val	missense_variant	5/5	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.568A>G	p.Ile190Val	missense_variant	5/5	1	NM_002358.4	ENSP00000296509	P1	Q13257-1
MAD2L1	ENST00000333047.9 linkuse as main transcript	c.*174A>G		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000332295		Q13257-2
MAD2L1	ENST00000512484.5 linkuse as main transcript	n.286A>G		non_coding_transcript_exon_variant	2/2	2
MAD2L1	ENST00000504707.1 linkuse as main transcript	c.*174A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	2		ENSP00000425702

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

553

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00601

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00429

AC:

1073

AN:

250180

Hom.:

AF XY:

0.00439

AC XY:

595

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.00706

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00562

AC:

8204

AN:

1459226

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

3949

AN XY:

725946

show subpopulations

Gnomad4 AFR exome

AF:

0.000958

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00193

Gnomad4 FIN exome

AF:

0.00418

Gnomad4 NFE exome

AF:

0.00662

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.00362

AC:

551

AN:

152282

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

235

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.00600

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00481

Hom.:

Bravo

AF:

0.00343

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00492

AC:

598

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.067

Eigen_PC

Benign

0.063

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0032

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.24

REVEL

Benign

0.21

Sift

Benign

0.67

Sift4G

Benign

0.73

Polyphen

0.32

Vest4

0.29

MVP

0.44

MPC

0.50

ClinPred

0.031

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.26

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