13-19467353-TAAAAAAAA-TA

Variant names:

• chr13-19467353-TAAAAAAA-T
• rs71092363
• NM_001395978.1:c.393-16_393-10delTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001395978.1(TPTE2):​c.393-16_393-10delTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,062,178 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: TPTE2 NM_001395978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

Genes affected

TPTE2 (HGNC:17299): (transmembrane phosphoinositide 3-phosphatase and tensin homolog 2) TPIP is a member of a large class of membrane-associated phosphatases with substrate specificity for the 3-position phosphate of inositol phospholipids.[supplied by OMIM, Jul 2002]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPTE2	NM_001395978.1	c.393-16_393-10delTTTTTTT		intron_variant	Intron 9 of 22	ENST00000697147.1	NP_001382907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPTE2	ENST00000697147.1	c.393-16_393-10delTTTTTTT		intron_variant	Intron 9 of 22		NM_001395978.1	ENSP00000513136.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000188 AC: 2 AN: 1062178 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 518820

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

African (AFR) AF: 0.00 AC: 0 AN: 22708

American (AMR) AF: 0.00 AC: 0 AN: 11016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15978

East Asian (EAS) AF: 0.00 AC: 0 AN: 25646

South Asian (SAS) AF: 0.0000248 AC: 1 AN: 40292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3676

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 863894

Other (OTH) AF: 0.00 AC: 0 AN: 43372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.002339), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs71092363; hg19: chr13-20041493;