rs74703632

Variant names:

• chr6-37638260-A-G
• rs74703632
• NM_153487.4:c.2721T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_153487.4(MDGA1):​c.2721T>C​(p.Asp907Asp) 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
• Publications: 0 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA1	NM_153487.4	MANE Select	c.2721T>C	p.Asp907Asp	synonymous	Exon 16 of 17	NP_705691.1	Q8NFP4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA1	ENST00000434837.8	TSL:1 MANE Select	c.2721T>C	p.Asp907Asp	synonymous	Exon 16 of 17	ENSP00000402584.2	Q8NFP4-1
	MDGA1	ENST00000505425.5	TSL:5	c.2721T>C	p.Asp907Asp	synonymous	Exon 16 of 16	ENSP00000422042.1	Q8NFP4-2
	MDGA1	ENST00000650466.1		c.2721T>C	p.Asp907Asp	synonymous	Exon 16 of 18	ENSP00000498018.1	A0A3B3IU48

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

GnomAD2 exomes AF: 0.00242 AC: 602 AN: 249064 AF XY: 0.00179

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 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

African (AFR) AF: 0.0347 AC: 1163 AN: 33476

American (AMR) AF: 0.00188 AC: 84 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5764

European-Non Finnish (NFE) AF: 0.000178 AC: 198 AN: 1111768

Other (OTH) AF: 0.00205 AC: 124 AN: 60358

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

African (AFR) AF: 0.0298 AC: 1232 AN: 41288

American (AMR) AF: 0.00368 AC: 56 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67922

Other (OTH) AF: 0.00569 AC: 12 AN: 2108

Alfa AF: 0.00447 Hom.: 5

Bravo AF: 0.0102

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		-0.0080
Mutation Taster		=100/0	polymorphism

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: rs74703632; hg19: chr6-37606036;