Genetic Variant NM_002361.4:c.1719C>A (chr19-35313292-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002361.4(MAG):c.1719C>A(p.Ser573Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MAG
NM_002361.4 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Variant links:

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]

MAG links:

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ACMG classification

Classification made for transcript

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=0.13340962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAG	NM_002361.4 link	c.1719C>A	p.Ser573Arg	missense_variant, splice_region_variant	Exon 11 of 11	ENST00000392213.8	NP_002352.1	P20916-1Q53ES7
MAG	NM_001199216.2 link	c.1644C>A	p.Ser548Arg	missense_variant, splice_region_variant	Exon 11 of 11		NP_001186145.1	P20916-3
MAG	NM_080600.3 link	c.*15C>A		splice_region_variant	Exon 12 of 12		NP_542167.1	P20916-2
MAG	NM_080600.3 link	c.*15C>A		3_prime_UTR_variant	Exon 12 of 12		NP_542167.1	P20916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAG	ENST00000392213.8 link	c.1719C>A	p.Ser573Arg	missense_variant, splice_region_variant	Exon 11 of 11	1	NM_002361.4	ENSP00000376048.2	P20916-1
MAG	ENST00000537831.2 link	c.1644C>A	p.Ser548Arg	missense_variant, splice_region_variant	Exon 11 of 11	1		ENSP00000440695.1	P20916-3
MAG	ENST00000361922.8 link	c.*15C>A		splice_region_variant	Exon 12 of 12	1		ENSP00000355234.4	P20916-2
MAG	ENST00000361922.8 link	c.*15C>A		3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000355234.4	P20916-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460324

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.27

Sift

Benign

0.22

T;T

Sift4G

Benign

0.089

T;T

Polyphen

0.83

P;.

Vest4

0.28

MutPred

0.23

Loss of phosphorylation at S573 (P = 0.0022);.;

MVP

0.91

MPC

0.59

ClinPred

0.71

GERP RS

-5.3

Varity_R

0.18

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over