6-37638289-G-A

Position:

• chr6-37638289-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_153487.4(MDGA1):​c.2692C>T​(p.Pro898Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDGA1 NM_153487.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.03

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07285252).
• BP6: Variant 6-37638289-G-A is Benign according to our data. Variant chr6-37638289-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3293805.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA1	NM_153487.4	c.2692C>T	p.Pro898Ser	missense_variant	16/17	ENST00000434837.8	NP_705691.1
MDGA1	XM_006715056.4	c.2692C>T	p.Pro898Ser	missense_variant	16/16		XP_006715119.1
MDGA1	XM_017010734.2	c.2692C>T	p.Pro898Ser	missense_variant	16/17		XP_016866223.1
MDGA1	XM_047418637.1	c.2524C>T	p.Pro842Ser	missense_variant	16/16		XP_047274593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA1	ENST00000434837.8	c.2692C>T	p.Pro898Ser	missense_variant	16/17	1	NM_153487.4	ENSP00000402584	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.026	T;.;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.54	N;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.63	N;.;N
REVEL	Benign	0.037
Sift	Benign	0.99	T;.;T
Sift4G	Benign	0.97	T;.;T
Polyphen		0.0	B;.;B
Vest4		0.12
MutPred		0.39		Gain of glycosylation at P898 (P = 0.0525);Gain of glycosylation at P898 (P = 0.0525);Gain of glycosylation at P898 (P = 0.0525);
MVP		0.093
MPC		0.28
ClinPred		0.050	T
GERP RS		3.6
Varity_R		0.023
gMVP		0.19

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: chr6-37606065;