Variant 4-120066707-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002358.4(MAD2L1):c.28G>A(p.Gly10Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000374 in 1,603,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MAD2L1
NM_002358.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAD2L1	NM_002358.4 linkuse as main transcript	c.28G>A	p.Gly10Arg	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.28G>A	p.Gly10Arg	missense_variant	1/5	1	NM_002358.4	ENSP00000296509	P1	Q13257-1
MAD2L1	ENST00000333047.9 linkuse as main transcript	c.28G>A	p.Gly10Arg	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000332295		Q13257-2
MAD2L1	ENST00000511295.1 linkuse as main transcript	n.115G>A		non_coding_transcript_exon_variant	1/2	2
MAD2L1	ENST00000504707.1 linkuse as main transcript	c.28G>A	p.Gly10Arg	missense_variant, NMD_transcript_variant	1/3	2		ENSP00000425702

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451442

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720380

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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 06, 2023

The c.28G>A (p.G10R) alteration is located in exon 1 (coding exon 1) of the MAD2L1 gene. This alteration results from a G to A substitution at nucleotide position 28, causing the glycine (G) at amino acid position 10 to be replaced by an arginine (R). 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

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.35

REVEL

Benign

0.22

Sift

Benign

0.43

Sift4G

Benign

0.50

Polyphen

0.99

Vest4

0.63

MutPred

0.34

Gain of MoRF binding (P = 0.0103);

MVP

0.73

MPC

0.77

ClinPred

0.96

GERP RS

5.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.2

Varity_R

0.51

gMVP

0.88

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