20-32824019-T-C

Variant names:

• chr20-32824019-T-C
• rs242553
• NM_012325.3:c.-3-1906T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012325.3(MAPRE1):​c.-3-1906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,208 control chromosomes in the GnomAD database, including 38,204 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (38204 hom., cov: 33)
• Consequence: MAPRE1 NM_012325.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 9 publications found

Genes affected

MAPRE1 (HGNC:6890): (microtubule associated protein RP/EB family member 1) The protein encoded by this gene was first identified by its binding to the APC protein which is often mutated in familial and sporadic forms of colorectal cancer. This protein localizes to microtubules, especially the growing ends, in interphase cells. During mitosis, the protein is associated with the centrosomes and spindle microtubules. The protein also associates with components of the dynactin complex and the intermediate chain of cytoplasmic dynein. Because of these associations, it is thought that this protein is involved in the regulation of microtubule structures and chromosome stability. This gene is a member of the RP/EB family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012325.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE1	NM_012325.3	MANE Select	c.-3-1906T>C		intron	N/A	NP_036457.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE1	ENST00000375571.6	TSL:1 MANE Select	c.-3-1906T>C		intron	N/A	ENSP00000364721.5

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104640 AN: 152088 Hom.: 38134 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.688 AC: 104770 AN: 152208 Hom.: 38204 Cov.: 33 AF XY: 0.688 AC XY: 51225 AN XY: 74402

African (AFR) AF: 0.914 AC: 37987 AN: 41570

American (AMR) AF: 0.661 AC: 10110 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2099 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5154 AN: 5178

South Asian (SAS) AF: 0.748 AC: 3612 AN: 4828

European-Finnish (FIN) AF: 0.538 AC: 5690 AN: 10578

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38062 AN: 67980

Other (OTH) AF: 0.626 AC: 1323 AN: 2114

Alfa AF: 0.627 Hom.: 3878

Bravo AF: 0.708

Asia WGS AF: 0.868 AC: 3018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs242553; hg19: chr20-31411825;