6-37643605-A-T

Variant names:

• chr6-37643605-A-T
• rs9462341
• NM_153487.4:c.2536+204T>A

Variant summary

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

The NM_153487.4(MDGA1):​c.2536+204T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,016 control chromosomes in the GnomAD database, including 23,130 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 0.54 (23130 hom., cov: 33)
• Consequence: MDGA1 NM_153487.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 3 publications found

Genes affected

MDGA1 (HGNC:19267): (MAM domain containing glycosylphosphatidylinositol anchor 1) This gene encodes a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is expressed predominantly in the developing nervous system. In addition to possessing several cell adhesion molecule-like domains, the mature protein has six Ig-like domains, a single fibronectin type III domain, a MAM domain and a C-terminal GPI-anchoring site. Studies in other mammals suggest this protein plays a role in cell adhesion, migration, and axon guidance and, in the developing brain, neuronal migration. In humans, this gene is associated with bipolar disorder and schizophrenia. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA1	NM_153487.4	c.2536+204T>A		intron_variant	Intron 14 of 16	ENST00000434837.8	NP_705691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA1	ENST00000434837.8	c.2536+204T>A		intron_variant	Intron 14 of 16	1	NM_153487.4	ENSP00000402584.2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82096 AN: 151898 Hom.: 23105 Cov.: 33

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.540 AC: 82152 AN: 152016 Hom.: 23130 Cov.: 33 AF XY: 0.548 AC XY: 40701 AN XY: 74278

African (AFR) AF: 0.359 AC: 14894 AN: 41450

American (AMR) AF: 0.601 AC: 9179 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1816 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2754 AN: 5154

South Asian (SAS) AF: 0.702 AC: 3387 AN: 4824

European-Finnish (FIN) AF: 0.649 AC: 6867 AN: 10578

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41358 AN: 67950

Other (OTH) AF: 0.542 AC: 1141 AN: 2104

Alfa AF: 0.576 Hom.: 3262

Bravo AF: 0.530

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.61
PhyloP100		-0.32
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: rs9462341; hg19: chr6-37611381;