6-37638287-C-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_153487.4(MDGA1):c.2694G>T(p.Pro898=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,611,886 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: MDGA1 NM_153487.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.38

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 6-37638287-C-A is Benign according to our data. Variant chr6-37638287-C-A is described in ClinVar as [Benign]. Clinvar id is 724732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.38 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA1	NM_153487.4	c.2694G>T	p.Pro898=	synonymous_variant	16/17	ENST00000434837.8
MDGA1	XM_006715056.4	c.2694G>T	p.Pro898=	synonymous_variant	16/16
MDGA1	XM_017010734.2	c.2694G>T	p.Pro898=	synonymous_variant	16/17
MDGA1	XM_047418637.1	c.2526G>T	p.Pro842=	synonymous_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA1	ENST00000434837.8	c.2694G>T	p.Pro898=	synonymous_variant	16/17	1	NM_153487.4	P1

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 268 AN: 152034 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000493 AC: 122 AN: 247502 Hom.: 0 AF XY: 0.000328 AC XY: 44 AN XY: 134198

Gnomad AFR exome AF: 0.00731

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000176 AC: 257 AN: 1459734 Hom.: 1 Cov.: 31 AF XY: 0.000143 AC XY: 104 AN XY: 726000

Gnomad4 AFR exome AF: 0.00640

Gnomad4 AMR exome AF: 0.000314

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.000365

GnomAD4 genome AF: 0.00176 AC: 268 AN: 152152 Hom.: 2 Cov.: 32 AF XY: 0.00167 AC XY: 124 AN XY: 74382

Gnomad4 AFR AF: 0.00600

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.0000428 Hom.: 0

Bravo AF: 0.00209

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	0.14
Dann	Benign	0.86

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: rs201158201; hg19: chr6-37606063;