7-1936820-GC-AT

Variant names:

• chr7-1936820-GC-AT
• NM_001013836.2:c.1673_1674delGCinsAT
• MAD1L1 p.Arg558His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001013836.2(MAD1L1):​c.1673_1674delGCinsAT​(p.Arg558His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.0000118 in 3 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R558C) has been classified as Uncertain significance.

• Frequency: GnomAD MNV: 𝑓 0.000012 Genomes: not found (cov: 34)
• Consequence: MAD1L1 NM_001013836.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.1673_1674delGCinsAT	p.Arg558His	missense	N/A	NP_001013858.1	Q9Y6D9-1
	MAD1L1	NM_001013837.2		c.1673_1674delGCinsAT	p.Arg558His	missense	N/A	NP_001013859.1	Q9Y6D9-1
	MAD1L1	NM_001304523.2		c.1673_1674delGCinsAT	p.Arg558His	missense	N/A	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.1673_1674delGCinsAT	p.Arg558His	missense	N/A	ENSP00000265854.7	Q9Y6D9-1
	MAD1L1	ENST00000406869.5	TSL:1	c.1673_1674delGCinsAT	p.Arg558His	missense	N/A	ENSP00000385334.1	Q9Y6D9-1
	ENSG00000286192	ENST00000651235.1		n.*4433_*4434delGCinsAT		non_coding_transcript_exon	Exon 22 of 24	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

GnomAD MNV AF: 0.0000118 AC: 3 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-1976456;