chr13-19467353-TAAAAAA-T

Variant names:

• chr13-19467353-TAAAAAA-T
• rs71092363
• NM_001395978.1:c.393-15_393-10delTTTTTT

Variant summary

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

The NM_001395978.1(TPTE2):​c.393-15_393-10delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,062,112 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: 0.000015 (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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395978.1. 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
	TPTE2	NM_001395978.1	MANE Select	c.393-15_393-10delTTTTTT		intron	N/A	NP_001382907.1
	TPTE2	NM_199254.3		c.393-15_393-10delTTTTTT		intron	N/A	NP_954863.2
	TPTE2	NM_130785.4		c.282-1795_282-1790delTTTTTT		intron	N/A	NP_570141.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPTE2	ENST00000697147.1	MANE Select	c.393-15_393-10delTTTTTT		intron	N/A	ENSP00000513136.1
	TPTE2	ENST00000390680.2	TSL:1	c.282-1795_282-1790delTTTTTT		intron	N/A	ENSP00000375098.2
	TPTE2	ENST00000696858.2		c.393-15_393-10delTTTTTT		intron	N/A	ENSP00000512931.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000151 AC: 16 AN: 1062112 Hom.: 0 AF XY: 0.0000193 AC XY: 10 AN XY: 518780

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

African (AFR) AF: 0.0000440 AC: 1 AN: 22706

American (AMR) AF: 0.0000908 AC: 1 AN: 11014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15976

East Asian (EAS) AF: 0.0000390 AC: 1 AN: 25646

South Asian (SAS) AF: 0.0000497 AC: 2 AN: 40280

European-Finnish (FIN) AF: 0.0000281 AC: 1 AN: 35594

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

European-Non Finnish (NFE) AF: 0.0000104 AC: 9 AN: 863854

Other (OTH) AF: 0.0000231 AC: 1 AN: 43366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;