Variant rs121908982 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_001013836.2(MAD1L1):c.175C>T(p.Arg59Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00445 in 1,613,878 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 20 hom. )

Consequence

MAD1L1
NM_001013836.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 5.79

Variant links:

Genes affected

MAD1L1 (HGNC:6762): (mitotic arrest deficient 1 like 1) MAD1L1 is a component of the mitotic spindle-assembly checkpoint that prevents the onset of anaphase until all chromosome are properly aligned at the metaphase plate. MAD1L1 functions as a homodimer and interacts with MAD2L1. MAD1L1 may play a role in cell cycle control and tumor suppression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MAD1L1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008932233).

BP6

Variant 7-2225526-G-A is Benign according to our data. Variant chr7-2225526-G-A is described in ClinVar as [Benign]. Clinvar id is 6920.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAD1L1	NM_001013836.2 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	4/19	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12 linkuse as main transcript	c.175C>T	p.Arg59Cys	missense_variant	4/19	1	NM_001013836.2	ENSP00000265854	P1	Q9Y6D9-1

Frequencies

GnomAD3 genomes

AF:

0.00297

AC:

452

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00544

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00308

AC:

767

AN:

249138

Hom.:

AF XY:

0.00329

AC XY:

445

AN XY:

135252

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00183

Gnomad NFE exome

AF:

0.00591

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00460

AC:

6724

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

3290

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00284

Gnomad4 NFE exome

AF:

0.00569

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.00297

AC:

452

AN:

152302

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00544

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00455

Hom.:

Bravo

AF:

0.00265

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000715

AC:

ESP6500EA

AF:

0.00556

AC:

ExAC

AF:

0.00350

AC:

424

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Prostate cancer, somatic

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 31, 2001

- -

Malignant tumor of prostate

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

Jan 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

T;T;T;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;.;.;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.0089

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.3

N;N;N;D

REVEL

Benign

0.27

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Uncertain

0.040

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.38

MVP

0.55

MPC

0.61

ClinPred

0.035

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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