6-37638307-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153487.4(MDGA1):c.2674T>G(p.Phe892Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDGA1 NM_153487.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.47

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA1	NM_153487.4	c.2674T>G	p.Phe892Val	missense_variant	16/17	ENST00000434837.8
MDGA1	XM_006715056.4	c.2674T>G	p.Phe892Val	missense_variant	16/16
MDGA1	XM_017010734.2	c.2674T>G	p.Phe892Val	missense_variant	16/17
MDGA1	XM_047418637.1	c.2506T>G	p.Phe836Val	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA1	ENST00000434837.8	c.2674T>G	p.Phe892Val	missense_variant	16/17	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: no assertion criteria provided

Submissions by phenotype

Acute megakaryoblastic leukemia;C1334655:Mediastinal germ cell tumor Uncertain:1

Uncertain significance, no assertion criteria provided

research

McDonnell Genome Institute, Washington University in St. Louis

Oct 22, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.0	M;.;M
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.7	D;.;D
REVEL	Benign	0.17
Sift	Uncertain	0.015	D;.;D
Sift4G	Uncertain	0.022	D;.;D
Polyphen		0.99	D;.;P
Vest4		0.64
MutPred		0.68		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.36
MPC		1.1
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.36
gMVP		0.80

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: rs864309493; hg19: chr6-37606083;