19-35309986-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_002361.4(MAG):​c.1344G>T​(p.Ser448Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAG
NM_002361.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP7
Synonymous conserved (PhyloP=-1.72 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGNM_002361.4 linkc.1344G>T p.Ser448Ser synonymous_variant Exon 8 of 11 ENST00000392213.8 NP_002352.1 P20916-1Q53ES7
MAGNM_001199216.2 linkc.1269G>T p.Ser423Ser synonymous_variant Exon 8 of 11 NP_001186145.1 P20916-3
MAGNM_080600.3 linkc.1344G>T p.Ser448Ser synonymous_variant Exon 8 of 12 NP_542167.1 P20916-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGENST00000392213.8 linkc.1344G>T p.Ser448Ser synonymous_variant Exon 8 of 11 1 NM_002361.4 ENSP00000376048.2 P20916-1
MAGENST00000537831.2 linkc.1269G>T p.Ser423Ser synonymous_variant Exon 8 of 11 1 ENSP00000440695.1 P20916-3
MAGENST00000361922.8 linkc.1344G>T p.Ser448Ser synonymous_variant Exon 8 of 12 1 ENSP00000355234.4 P20916-2
MAGENST00000593348.1 linkn.181G>T non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461670
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727158
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.053
DANN
Benign
0.88

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: chr19-35800889; API