NM_001013836.2:c.1790C>T

Variant names:

• chr7-1936704-G-A
• rs373139029
• NM_001013836.2:c.1790C>T

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1790C>T​(p.Ser597Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,555,820 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: MAD1L1 NM_001013836.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42
• 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=0.06528416).

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.1790C>T	p.Ser597Leu	missense	Exon 17 of 19	NP_001013858.1	Q9Y6D9-1
	MAD1L1	NM_001013837.2		c.1790C>T	p.Ser597Leu	missense	Exon 17 of 19	NP_001013859.1	Q9Y6D9-1
	MAD1L1	NM_001304523.2		c.1790C>T	p.Ser597Leu	missense	Exon 16 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.1790C>T	p.Ser597Leu	missense	Exon 17 of 19	ENSP00000265854.7	Q9Y6D9-1
	MAD1L1	ENST00000406869.5	TSL:1	c.1790C>T	p.Ser597Leu	missense	Exon 17 of 19	ENSP00000385334.1	Q9Y6D9-1
	ENSG00000286192	ENST00000651235.1		n.*4550C>T		non_coding_transcript_exon	Exon 22 of 24	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152234 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000166 AC: 26 AN: 156258 AF XY: 0.000225

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000391

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000346

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000177 AC: 249 AN: 1403586 Hom.: 1 Cov.: 32 AF XY: 0.000201 AC XY: 139 AN XY: 693178

African (AFR) AF: 0.000125 AC: 4 AN: 32092

American (AMR) AF: 0.0000819 AC: 3 AN: 36640

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 3 AN: 25224

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36406

South Asian (SAS) AF: 0.000226 AC: 18 AN: 79694

European-Finnish (FIN) AF: 0.0000214 AC: 1 AN: 46816

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5508

European-Non Finnish (NFE) AF: 0.000194 AC: 210 AN: 1082980

Other (OTH) AF: 0.000137 AC: 8 AN: 58226

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152234 Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6 AN XY: 74372

African (AFR) AF: 0.0000724 AC: 3 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00318 AC: 1 AN: 314

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000225 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000495 AC: 4

ExAC AF: 0.0000700 AC: 8

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	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.099
Sift	Benign	0.37	T
Sift4G	Benign	0.067	T
Polyphen		0.97	D
Vest4		0.60
MVP		0.40
MPC		0.14
ClinPred		0.20	T
GERP RS		4.8
Varity_R		0.095
gMVP		0.28
Mutation Taster		=72/28	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: rs373139029; hg19: chr7-1976340;