chr7-1898364-C-T

Variant names:

• chr7-1898364-C-T
• rs200433567
• NM_001013836.2:c.1834G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001013836.2(MAD1L1):​c.1834G>A​(p.Glu612Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000942 in 1,613,938 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: 𝑓 0.00049 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: MAD1L1 NM_001013836.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.69
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• familial prostate carcinoma

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000286192 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06470892).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013836.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	NM_001013836.2	MANE Select	c.1834G>A	p.Glu612Lys	missense	Exon 18 of 19	NP_001013858.1	Q9Y6D9-1
	MAD1L1	NM_001013837.2		c.1834G>A	p.Glu612Lys	missense	Exon 18 of 19	NP_001013859.1	Q9Y6D9-1
	MAD1L1	NM_001304523.2		c.1834G>A	p.Glu612Lys	missense	Exon 17 of 18	NP_001291452.1	Q9Y6D9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	ENST00000265854.12	TSL:1 MANE Select	c.1834G>A	p.Glu612Lys	missense	Exon 18 of 19	ENSP00000265854.7	Q9Y6D9-1
	MAD1L1	ENST00000406869.5	TSL:1	c.1834G>A	p.Glu612Lys	missense	Exon 18 of 19	ENSP00000385334.1	Q9Y6D9-1
	ENSG00000286192	ENST00000651235.1		n.*4594G>A		non_coding_transcript_exon	Exon 23 of 24	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00179

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 249010 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000534 AC: 78 AN: 1461670 Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 34 AN XY: 727124

African (AFR) AF: 0.00131 AC: 44 AN: 33478

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111960

Other (OTH) AF: 0.000149 AC: 9 AN: 60390

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000457 AC XY: 34 AN XY: 74456

African (AFR) AF: 0.00178 AC: 74 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.000650

ESP6500AA AF: 0.00167 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000132 AC: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		5.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.059	T
Polyphen		1.0	D
Vest4		0.83
MVP		0.61
MPC		0.44
ClinPred		0.20	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.87
gMVP		0.57
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs200433567; hg19: chr7-1938000;