2-32532171-G-GTGTGTGTGTGTGT

Variant names:

• chr2-32532171-G-GTGTGTGTGTGTGT
• rs35999329
• NM_016252.4:c.12291+620_12291+621insTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016252.4(BIRC6):​c.12291+620_12291+621insTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. 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. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00070 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0074 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BIRC6 NM_016252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931
• Publications: 2 publications found

Genes affected

BIRC6 (HGNC:13516): (baculoviral IAP repeat containing 6) This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination. [provided by RefSeq, Jul 2008]

MIR558 (HGNC:32814): (microRNA 558) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016252.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	NM_016252.4	MANE Select	c.12291+620_12291+621insTGTGTGTGTGTGT		intron	N/A	NP_057336.3
	MIR558	NR_030285.1		n.19_20insTGTGTGTGTGTGT		non_coding_transcript_exon	Exon 1 of 1
	BIRC6	NM_001378125.1		c.12288+620_12288+621insTGTGTGTGTGTGT		intron	N/A	NP_001365054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	ENST00000421745.7	TSL:1 MANE Select	c.12291+620_12291+621insTGTGTGTGTGTGT		intron	N/A	ENSP00000393596.2
	MIR558	ENST00000384920.1	TSL:6	n.19_20insTGTGTGTGTGTGT		non_coding_transcript_exon	Exon 1 of 1
	BIRC6	ENST00000700518.1		c.12240+620_12240+621insTGTGTGTGTGTGT		intron	N/A	ENSP00000515025.1

Frequencies

GnomAD3 genomes AF: 0.000690 AC: 103 AN: 149270 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000469

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.000267

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.000397

Gnomad SAS AF: 0.00107

Gnomad FIN AF: 0.000885

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000893

Gnomad OTH AF: 0.000977

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00742 AC: 2783 AN: 374912 Hom.: 0 Cov.: 0 AF XY: 0.00733 AC XY: 1566 AN XY: 213720

African (AFR) AF: 0.00734 AC: 75 AN: 10212

American (AMR) AF: 0.0105 AC: 373 AN: 35614

Ashkenazi Jewish (ASJ) AF: 0.0134 AC: 154 AN: 11472

East Asian (EAS) AF: 0.00292 AC: 38 AN: 13022

South Asian (SAS) AF: 0.00761 AC: 501 AN: 65834

European-Finnish (FIN) AF: 0.0157 AC: 494 AN: 31398

Middle Eastern (MID) AF: 0.00698 AC: 9 AN: 1290

European-Non Finnish (NFE) AF: 0.00550 AC: 1044 AN: 189760

Other (OTH) AF: 0.00582 AC: 95 AN: 16310

GnomAD4 genome AF: 0.000696 AC: 104 AN: 149386 Hom.: 1 Cov.: 0 AF XY: 0.000837 AC XY: 61 AN XY: 72890

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

African (AFR) AF: 0.000468 AC: 19 AN: 40636

American (AMR) AF: 0.000266 AC: 4 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3438

East Asian (EAS) AF: 0.000596 AC: 3 AN: 5032

South Asian (SAS) AF: 0.00107 AC: 5 AN: 4656

European-Finnish (FIN) AF: 0.000885 AC: 9 AN: 10172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000893 AC: 60 AN: 67186

Other (OTH) AF: 0.000966 AC: 2 AN: 2070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000038658), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0148 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs35999329; hg19: chr2-32757238;