3-184711345-ATCCTCCTCCTCC-ATCCTCCTCCTCCTCCTCCTCCTCCTCC

Variant names:

• chr3-184711345-A-ATCCTCCTCCTCCTCC
• rs34995413
• NM_022149.5:c.462_476dupGGAGGAGGAGGAGGA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_022149.5(MAGEF1):​c.462_476dupGGAGGAGGAGGAGGA​(p.Glu154_Glu158dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 150,448 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 0)
• Consequence: MAGEF1 NM_022149.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 12 publications found

Genes affected

MAGEF1 (HGNC:29639): (MAGE family member F1) This intronless gene encodes a member of the MAGE superfamily. It is ubiquitously expressed in normal tissues and in tumor cells. This gene includes a microsatellite repeat in the coding region. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_022149.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEF1	NM_022149.5	c.462_476dupGGAGGAGGAGGAGGA	p.Glu154_Glu158dup	disruptive_inframe_insertion	Exon 1 of 1	ENST00000317897.5	NP_071432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEF1	ENST00000317897.5	c.462_476dupGGAGGAGGAGGAGGA	p.Glu154_Glu158dup	disruptive_inframe_insertion	Exon 1 of 1	6	NM_022149.5	ENSP00000315064.3

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 AN: 150448 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000245

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 88

GnomAD4 genome AF: 0.00000665 AC: 1 AN: 150448 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 1 AN XY: 73408

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000245 AC: 1 AN: 40870

American (AMR) AF: 0.00 AC: 0 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67488

Other (OTH) AF: 0.00 AC: 0 AN: 2076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 3040

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=82/18	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34995413; hg19: chr3-184429133;