rs9462343

Positions:

• chr6-37653000-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153487.4(MDGA1):​c.983-660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,088 control chromosomes in the GnomAD database, including 7,132 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 0.28 (7132 hom., cov: 33)
• Consequence: MDGA1 NM_153487.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA1	NM_153487.4	c.983-660C>T		intron_variant		ENST00000434837.8	NP_705691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA1	ENST00000434837.8	c.983-660C>T		intron_variant		1	NM_153487.4	ENSP00000402584	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42965 AN: 151970 Hom.: 7110 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.283 AC: 43020 AN: 152088 Hom.: 7132 Cov.: 33 AF XY: 0.278 AC XY: 20685 AN XY: 74338

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.299

Alfa AF: 0.231 Hom.: 2062

Bravo AF: 0.294

Asia WGS AF: 0.179 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs9462343; hg19: chr6-37620776;