6-37635931-C-T

Variant names:

• chr6-37635931-C-T
• rs12191311
• NM_153487.4:c.*1437G>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.*1437G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 395,542 control chromosomes in the GnomAD database, including 28,597 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 0.31 (9101 hom., cov: 33)
  • Exomes 𝑓: 0.39 (19496 hom.)
• Consequence: MDGA1 NM_153487.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153487.4. 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
	MDGA1	NM_153487.4	MANE Select	c.*1437G>A		3_prime_UTR	Exon 17 of 17	NP_705691.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA1	ENST00000434837.8	TSL:1 MANE Select	c.*1437G>A		3_prime_UTR	Exon 17 of 17	ENSP00000402584.2
	MDGA1	ENST00000373401.2	TSL:2	n.2926G>A		non_coding_transcript_exon	Exon 3 of 3
	MDGA1	ENST00000681472.1		n.*2255G>A		non_coding_transcript_exon	Exon 17 of 17	ENSP00000506519.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47316 AN: 152036 Hom.: 9106 Cov.: 33

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.389 AC: 94637 AN: 243388 Hom.: 19496 Cov.: 0 AF XY: 0.389 AC XY: 47935 AN XY: 123292

African (AFR) AF: 0.0863 AC: 616 AN: 7138

American (AMR) AF: 0.292 AC: 2136 AN: 7314

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 2631 AN: 9176

East Asian (EAS) AF: 0.222 AC: 5035 AN: 22698

South Asian (SAS) AF: 0.255 AC: 552 AN: 2168

European-Finnish (FIN) AF: 0.452 AC: 9473 AN: 20940

Middle Eastern (MID) AF: 0.304 AC: 391 AN: 1286

European-Non Finnish (NFE) AF: 0.436 AC: 68216 AN: 156460

Other (OTH) AF: 0.345 AC: 5587 AN: 16208

GnomAD4 genome AF: 0.311 AC: 47296 AN: 152154 Hom.: 9101 Cov.: 33 AF XY: 0.311 AC XY: 23092 AN XY: 74368

African (AFR) AF: 0.0882 AC: 3662 AN: 41528

American (AMR) AF: 0.301 AC: 4606 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5176

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4824

European-Finnish (FIN) AF: 0.441 AC: 4655 AN: 10566

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30058 AN: 67984

Other (OTH) AF: 0.278 AC: 588 AN: 2112

Alfa AF: 0.371 Hom.: 22797

Bravo AF: 0.291

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		0.15
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: rs12191311; hg19: chr6-37603707;