rs765679969

Variant names:

• chrX-16170676-GTCC-G
• rs765679969
• NM_001277307.2:c.300_302delCTC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

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-AS1 (HGNC:56739): (MAGEB17 antisense RNA 1)

ACMG classification

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 VariationId is 2660064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277307.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB17	NM_001277307.2	MANE Select	c.300_302delCTC	p.Ser101del	disruptive_inframe_deletion	Exon 2 of 2	NP_001264236.1	A8MXT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB17	ENST00000400004.6	TSL:2 MANE Select	c.300_302delCTC	p.Ser101del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000382884.2	A8MXT2
	MAGEB17	ENST00000400003.1	TSL:5	c.300_302delCTC	p.Ser101del	disruptive_inframe_deletion	Exon 3 of 3	ENSP00000382883.1	A8MXT2
	MAGEB17-AS1	ENST00000435789.1	TSL:5	n.191_193delGGA		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.000214 AC: 24 AN: 112207 Hom.: 0 Cov.: 23

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: 19 AN: 108382 AF XY: 0.000303

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.: 0 AF XY: 0.000328 AC XY: 113 AN XY: 344741

African (AFR) AF: 0.00 AC: 0 AN: 24917

American (AMR) AF: 0.0000358 AC: 1 AN: 27913

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18640

East Asian (EAS) AF: 0.00 AC: 0 AN: 27135

South Asian (SAS) AF: 0.0000200 AC: 1 AN: 49882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4089

European-Non Finnish (NFE) AF: 0.000410 AC: 336 AN: 819671

Other (OTH) AF: 0.000180 AC: 8 AN: 44396

GnomAD4 genome AF: 0.000214 AC: 24 AN: 112259 Hom.: 0 Cov.: 23 AF XY: 0.000174 AC XY: 6 AN XY: 34443

African (AFR) AF: 0.000129 AC: 4 AN: 30891

American (AMR) AF: 0.00 AC: 0 AN: 10710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3542

South Asian (SAS) AF: 0.00 AC: 0 AN: 2676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000376 AC: 20 AN: 53183

Other (OTH) AF: 0.00 AC: 0 AN: 1535

Alfa AF: 0.000260 Hom.: 2

Bravo AF: 0.000283

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
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

Other links and lift over

dbSNP: rs765679969; hg19: chrX-16188799;