6-37638260-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_153487.4(MDGA1):c.2721T>C(p.Asp907=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,613,090 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0087 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (18 hom.)
• Consequence: MDGA1 NM_153487.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00800

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-37638260-A-G is Benign according to our data. Variant chr6-37638260-A-G is described in ClinVar as [Benign]. Clinvar id is 791448.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.008 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00866 (1313/151630) while in subpopulation AFR AF= 0.0298 (1232/41288). AF 95% confidence interval is 0.0285. There are 20 homozygotes in gnomad4. There are 625 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA1	NM_153487.4	c.2721T>C	p.Asp907=	synonymous_variant	16/17	ENST00000434837.8
MDGA1	XM_006715056.4	c.2721T>C	p.Asp907=	synonymous_variant	16/16
MDGA1	XM_017010734.2	c.2721T>C	p.Asp907=	synonymous_variant	16/17
MDGA1	XM_047418637.1	c.2553T>C	p.Asp851=	synonymous_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA1	ENST00000434837.8	c.2721T>C	p.Asp907=	synonymous_variant	16/17	1	NM_153487.4	P1

Frequencies

GnomAD3 genomes AF: 0.00865 AC: 1311 AN: 151514 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00368

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00242 AC: 602 AN: 249064 Hom.: 8 AF XY: 0.00179 AC XY: 242 AN XY: 135116

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.00177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000992

GnomAD4 exome AF: 0.00109 AC: 1586 AN: 1461460 Hom.: 18 Cov.: 31 AF XY: 0.000895 AC XY: 651 AN XY: 727016

Gnomad4 AFR exome AF: 0.0347

Gnomad4 AMR exome AF: 0.00188

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000178

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00866 AC: 1313 AN: 151630 Hom.: 20 Cov.: 32 AF XY: 0.00844 AC XY: 625 AN XY: 74068

Gnomad4 AFR AF: 0.0298

Gnomad4 AMR AF: 0.00368

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00467 Hom.: 3

Bravo AF: 0.0102

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000533

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	4.2
Dann	Benign	0.66

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: rs74703632; hg19: chr6-37606036;