6-37638555-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_153487.4(MDGA1):c.2649C>T(p.Ser883=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,613,972 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (21 hom.)
• Consequence: MDGA1 NM_153487.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 6-37638555-G-A is Benign according to our data. Variant chr6-37638555-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.4 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA1	NM_153487.4	c.2649C>T	p.Ser883=	synonymous_variant	15/17	ENST00000434837.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA1	ENST00000434837.8	c.2649C>T	p.Ser883=	synonymous_variant	15/17	1	NM_153487.4	P1

Frequencies

GnomAD3 genomes AF: 0.000801 AC: 122 AN: 152246 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00199 AC: 495 AN: 248992 Hom.: 7 AF XY: 0.00244 AC XY: 330 AN XY: 135126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.000890

Gnomad SAS exome AF: 0.00951

Gnomad FIN exome AF: 0.000279

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00126 AC: 1838 AN: 1461608 Hom.: 21 Cov.: 31 AF XY: 0.00157 AC XY: 1145 AN XY: 727088

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00306

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.00963

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000633

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.000807 AC: 123 AN: 152364 Hom.: 0 Cov.: 32 AF XY: 0.000886 AC XY: 66 AN XY: 74506

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00973

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000764

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00123 Hom.: 1

Bravo AF: 0.000684

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

MDGA1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	11
Dann	Benign	0.77

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: rs201772848; hg19: chr6-37606331;