13-19467353-TAAAAAAAA-TAAAAA

Variant names:

• chr13-19467353-TAAA-T
• rs71092363
• NM_001395978.1:c.393-12_393-10delTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001395978.1(TPTE2):​c.393-12_393-10delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,160,252 control chromosomes in the GnomAD database, including 109 homozygotes. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.024 (100 hom., cov: 0)
  • Exomes 𝑓: 0.022 (9 hom.)
• Consequence: TPTE2 NM_001395978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

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.393-12_393-10delTTT		intron	N/A	NP_001382907.1	Q6XPS3-1
	TPTE2	NM_199254.3		c.393-12_393-10delTTT		intron	N/A	NP_954863.2	Q6XPS3-1
	TPTE2	NM_130785.4		c.282-1792_282-1790delTTT		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.393-12_393-10delTTT		intron	N/A	ENSP00000513136.1	Q6XPS3-1
	TPTE2	ENST00000390680.2	TSL:1	c.282-1792_282-1790delTTT		intron	N/A	ENSP00000375098.2	Q6XPS3-3
	TPTE2	ENST00000696858.2		c.393-12_393-10delTTT		intron	N/A	ENSP00000512931.1	Q6XPS3-1

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3146 AN: 131638 Hom.: 100 Cov.: 0

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00934

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.000440

Gnomad SAS AF: 0.00696

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00730

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.0199

GnomAD2 exomes AF: 0.0401 AC: 1310 AN: 32670 AF XY: 0.0449

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0676

Gnomad ASJ exome AF: 0.0797

Gnomad EAS exome AF: 0.0393

Gnomad FIN exome AF: 0.00920

Gnomad NFE exome AF: 0.0329

Gnomad OTH exome AF: 0.0386

GnomAD4 exome AF: 0.0222 AC: 22861 AN: 1028608 Hom.: 9 AF XY: 0.0238 AC XY: 11951 AN XY: 502240

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

African (AFR) AF: 0.102 AC: 2252 AN: 22146

American (AMR) AF: 0.0584 AC: 620 AN: 10610

Ashkenazi Jewish (ASJ) AF: 0.0535 AC: 832 AN: 15544

East Asian (EAS) AF: 0.0298 AC: 731 AN: 24514

South Asian (SAS) AF: 0.0500 AC: 1952 AN: 39056

European-Finnish (FIN) AF: 0.0295 AC: 1021 AN: 34646

Middle Eastern (MID) AF: 0.0301 AC: 108 AN: 3584

European-Non Finnish (NFE) AF: 0.0168 AC: 14064 AN: 836514

Other (OTH) AF: 0.0305 AC: 1281 AN: 41994

⚠️ 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 AF: 0.0239 AC: 3151 AN: 131644 Hom.: 100 Cov.: 0 AF XY: 0.0241 AC XY: 1516 AN XY: 62948

African (AFR) AF: 0.0765 AC: 2781 AN: 36340

American (AMR) AF: 0.00933 AC: 124 AN: 13288

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 69 AN: 3192

East Asian (EAS) AF: 0.000442 AC: 2 AN: 4530

South Asian (SAS) AF: 0.00675 AC: 27 AN: 3998

European-Finnish (FIN) AF: 0.00273 AC: 18 AN: 6598

Middle Eastern (MID) AF: 0.00806 AC: 2 AN: 248

European-Non Finnish (NFE) AF: 0.00151 AC: 92 AN: 60812

Other (OTH) AF: 0.0198 AC: 36 AN: 1820

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs71092363; hg19: chr13-20041493;