chr13-19467350-ATAT-AT

Variant names:

• chr13-19467349-AAT-A
• rs765410775
• NM_001395978.1:c.393-7_393-6delAT

Variant summary

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

The NM_001395978.1(TPTE2):​c.393-7_393-6delAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPTE2 NM_001395978.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• 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 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPTE2	NM_001395978.1	MANE Select	c.393-7_393-6delAT		splice_region intron	N/A	NP_001382907.1	Q6XPS3-1
	TPTE2	NM_199254.3		c.393-7_393-6delAT		splice_region intron	N/A	NP_954863.2	Q6XPS3-1
	TPTE2	NM_130785.4		c.282-1787_282-1786delAT		intron	N/A	NP_570141.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPTE2	ENST00000697147.1	MANE Select	c.393-7_393-6delAT		splice_region intron	N/A	ENSP00000513136.1	Q6XPS3-1
	TPTE2	ENST00000390680.2	TSL:1	c.282-1787_282-1786delAT		intron	N/A	ENSP00000375098.2	Q6XPS3-3
	TPTE2	ENST00000696858.2		c.393-7_393-6delAT		splice_region intron	N/A	ENSP00000512931.1	Q6XPS3-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 65210 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000215 AC: 28 AN: 1303474 Hom.: 0 AF XY: 0.0000295 AC XY: 19 AN XY: 643048

⚠️ 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: 27222

American (AMR) AF: 0.0000536 AC: 1 AN: 18652

Ashkenazi Jewish (ASJ) AF: 0.0000486 AC: 1 AN: 20588

East Asian (EAS) AF: 0.00 AC: 0 AN: 34362

South Asian (SAS) AF: 0.0000787 AC: 5 AN: 63520

European-Finnish (FIN) AF: 0.0000859 AC: 4 AN: 46564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5074

European-Non Finnish (NFE) AF: 0.0000145 AC: 15 AN: 1033904

Other (OTH) AF: 0.0000373 AC: 2 AN: 53588

⚠️ 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 Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 65210 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 31490

African (AFR) AF: 0.00 AC: 0 AN: 21430

American (AMR) AF: 0.00 AC: 0 AN: 4358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1704

East Asian (EAS) AF: 0.00 AC: 0 AN: 1970

South Asian (SAS) AF: 0.00 AC: 0 AN: 1006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 184

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 29010

Other (OTH) AF: 0.00 AC: 0 AN: 768

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs765410775; hg19: chr13-20041489;