19-35295622-G-C

Position:

• chr19-35295622-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002361.4(MAG):​c.56G>C​(p.Gly19Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAG NM_002361.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25

Genes affected

MAG (HGNC:6783): (myelin associated glycoprotein) The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24780467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAG	NM_002361.4	c.56G>C	p.Gly19Ala	missense_variant	4/11	ENST00000392213.8	NP_002352.1
MAG	NM_080600.3	c.56G>C	p.Gly19Ala	missense_variant	4/12		NP_542167.1
MAG	NM_001199216.2	c.-20G>C		5_prime_UTR_variant	4/11		NP_001186145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8	c.56G>C	p.Gly19Ala	missense_variant	4/11	1	NM_002361.4	ENSP00000376048.2

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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.56G>C (p.G19A) alteration is located in exon 4 (coding exon 2) of the MAG gene. This alteration results from a G to C substitution at nucleotide position 56, causing the glycine (G) at amino acid position 19 to be replaced by an alanine (A). 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	0.14
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;.;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.28	N;N;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.48	N;N;.;.
REVEL	Benign	0.14
Sift	Benign	0.31	T;T;.;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.47	P;.;.;.
Vest4		0.19
MutPred		0.57		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.62
MPC		0.47
ClinPred		0.86	D
GERP RS		5.4
Varity_R		0.14
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35786525;