Genetic Variant MAG:p.Ser39Phe (chr19-35295682-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002361.4(MAG):c.116C>T(p.Ser39Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAG
NM_002361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.54

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex hereditary spastic paraplegia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 75
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

MAG links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2629612).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002361.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAG	NM_002361.4	MANE Select	c.116C>T	p.Ser39Phe	missense	Exon 4 of 11	NP_002352.1	P20916-1
MAG	NM_001199216.2		c.41C>T	p.Ser14Phe	missense	Exon 4 of 11	NP_001186145.1	P20916-3
MAG	NM_080600.3		c.116C>T	p.Ser39Phe	missense	Exon 4 of 12	NP_542167.1	P20916-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAG	ENST00000392213.8	TSL:1 MANE Select	c.116C>T	p.Ser39Phe	missense	Exon 4 of 11	ENSP00000376048.2	P20916-1
MAG	ENST00000537831.2	TSL:1	c.41C>T	p.Ser14Phe	missense	Exon 4 of 11	ENSP00000440695.1	P20916-3
MAG	ENST00000361922.8	TSL:1	c.116C>T	p.Ser39Phe	missense	Exon 4 of 12	ENSP00000355234.4	P20916-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460692

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726746

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111972

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 75 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.041

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PhyloP100

3.5

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.12

REVEL

Benign

0.19

Sift

Benign

0.15

Sift4G

Benign

0.093

Polyphen

0.94

Vest4

0.41

MutPred

0.47

Gain of glycosylation at T36 (P = 0.1469)

MVP

0.62

MPC

0.94

ClinPred

0.82

GERP RS

5.4

Varity_R

0.19

gMVP

0.70

Mutation Taster

=45/55

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over