Variant 7-1898239-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001013836.2(MAD1L1):c.1959G>A(p.Ser653=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,613,760 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 75 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 77 hom. )

Consequence

MAD1L1
NM_001013836.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.201

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 7-1898239-C-T is Benign according to our data. Variant chr7-1898239-C-T is described in ClinVar as [Benign]. Clinvar id is 785208.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.201 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAD1L1	NM_001013836.2 linkuse as main transcript	c.1959G>A	p.Ser653=	synonymous_variant	18/19	ENST00000265854.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAD1L1	ENST00000265854.12 linkuse as main transcript	c.1959G>A	p.Ser653=	synonymous_variant	18/19	1	NM_001013836.2	P1	Q9Y6D9-1

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2730

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0621

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00470

AC:

1165

AN:

247716

Hom.:

AF XY:

0.00355

AC XY:

478

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.0646

Gnomad AMR exome

AF:

0.00326

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000428

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.00200

AC:

2923

AN:

1461502

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1325

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.0653

Gnomad4 AMR exome

AF:

0.00372

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000237

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.0180

AC:

2737

AN:

152258

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1284

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0621

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00714

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000475

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.1

DANN

Benign

0.60

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