Variant rs142334011 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000392213.8(MAG):c.228G>A(p.Ser76=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,613,682 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S76S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 16 hom. )

Consequence

MAG
ENST00000392213.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 19-35295794-G-A is Benign according to our data. Variant chr19-35295794-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00193 (293/152084) while in subpopulation SAS AF= 0.00603 (29/4812). AF 95% confidence interval is 0.00431. There are 2 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAG	NM_002361.4 linkuse as main transcript	c.228G>A	p.Ser76=	synonymous_variant	4/11	ENST00000392213.8	NP_002352.1
MAG	NM_001199216.2 linkuse as main transcript	c.153G>A	p.Ser51=	synonymous_variant	4/11		NP_001186145.1
MAG	NM_080600.3 linkuse as main transcript	c.228G>A	p.Ser76=	synonymous_variant	4/12		NP_542167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8 linkuse as main transcript	c.228G>A	p.Ser76=	synonymous_variant	4/11	1	NM_002361.4	ENSP00000376048	P1	P20916-1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

296

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00602

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00294

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00257

AC:

645

AN:

250946

Hom.:

AF XY:

0.00303

AC XY:

411

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00526

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00335

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00245

AC:

3587

AN:

1461598

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

1945

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00524

Gnomad4 FIN exome

AF:

0.000395

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00193

AC:

293

AN:

152084

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

147

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00603

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.00185

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00447

EpiControl

AF:

0.00474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	MAG: BP4, BP7, BS2 -

Hereditary spastic paraplegia 75

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.1

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over