6-37643865-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153487.4(MDGA1):c.2480C>A(p.Ala827Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDGA1 NM_153487.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27735996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA1	NM_153487.4	c.2480C>A	p.Ala827Asp	missense_variant	14/17	ENST00000434837.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA1	ENST00000434837.8	c.2480C>A	p.Ala827Asp	missense_variant	14/17	1	NM_153487.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2022

The c.2480C>A (p.A827D) alteration is located in exon 14 (coding exon 14) of the MDGA1 gene. This alteration results from a C to A substitution at nucleotide position 2480, causing the alanine (A) at amino acid position 827 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.071	T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	M;.;M
MutationTaster	Benign	0.57	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N;.;N
REVEL	Benign	0.11
Sift	Benign	0.035	D;.;D
Sift4G	Uncertain	0.059	T;.;T
Polyphen		0.077	B;.;P
Vest4		0.58
MutPred		0.51		Gain of phosphorylation at Y825 (P = 0.1032);Gain of phosphorylation at Y825 (P = 0.1032);Gain of phosphorylation at Y825 (P = 0.1032);
MVP		0.12
MPC		0.74
ClinPred		0.79	D
GERP RS		4.8
Varity_R		0.23
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-37611641;