Genetic Variant MAGEB17:p.Ser101del (chrX-16170676-GTCC-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The NM_001277307.2(MAGEB17):c.300_302delCTC(p.Ser101del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,165,644 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 119 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00033 ( 0 hom. 113 hem. )

Consequence

MAGEB17
NM_001277307.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

MAGEB17 (HGNC:17418): (MAGE family member B17) Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MAGEB17 links:

ENSG00000238178 (HGNC:56739): (MAGEB17 antisense RNA 1)

ENSG00000238178 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001277307.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant X-16170676-GTCC-G is Benign according to our data. Variant chrX-16170676-GTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2660064.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB17	NM_001277307.2 link	c.300_302delCTC	p.Ser101del	disruptive_inframe_deletion	Exon 2 of 2	ENST00000400004.6	NP_001264236.1	A8MXT2
MAGEB17	XM_047442355.1 link	c.300_302delCTC	p.Ser101del	disruptive_inframe_deletion	Exon 2 of 2		XP_047298311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAGEB17	ENST00000400004.6 link	c.300_302delCTC	p.Ser101del	disruptive_inframe_deletion	Exon 2 of 2	2	NM_001277307.2	ENSP00000382884.2	A8MXT2
MAGEB17	ENST00000400003.1 link	c.300_302delCTC	p.Ser101del	disruptive_inframe_deletion	Exon 3 of 3	5		ENSP00000382883.1	A8MXT2
ENSG00000238178	ENST00000435789.1 link	n.191_193delGGA		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.000214

AC:

AN:

112207

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000175

AC:

AN:

108382

AF XY:

0.000303

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000430

Gnomad OTH exome

AF:

0.000313

GnomAD4 exome

AF:

0.000328

AC:

346

AN:

1053385

Hom.:

AF XY:

0.000328

AC XY:

113

AN XY:

344741

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

24917

Gnomad4 AMR exome

AF:

0.0000358

AC:

AN:

27913

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

18640

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

27135

Gnomad4 SAS exome

AF:

0.0000200

AC:

AN:

49882

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

36742

Gnomad4 NFE exome

AF:

0.000410

AC:

336

AN:

819671

Gnomad4 Remaining exome

AF:

0.000180

AC:

AN:

44396

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000214

AC:

AN:

112259

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34443

show subpopulations

Gnomad4 AFR

AF:

0.000129

AC:

0.000129488

AN:

0.000129488

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000376

AC:

0.00037606

AN:

0.00037606

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000283

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MAGEB17: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=93/7

polymorphism

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