NM_001395978.1:c.-43-20872C>G

Variant names:

• chr13-19524149-G-C
• rs2451078
• NM_001395978.1:c.-43-20872C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395978.1(TPTE2):​c.-43-20872C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 152,238 control chromosomes in the GnomAD database, including 66,624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.93 (66624 hom., cov: 32)
• Consequence: TPTE2 NM_001395978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPTE2	NM_001395978.1	MANE Select	c.-43-20872C>G		intron	N/A	NP_001382907.1
	TPTE2	NM_199254.3		c.-44+12447C>G		intron	N/A	NP_954863.2
	TPTE2	NM_130785.4		c.-44+12447C>G		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.-43-20872C>G		intron	N/A	ENSP00000513136.1
	TPTE2	ENST00000390680.2	TSL:1	c.-44+12447C>G		intron	N/A	ENSP00000375098.2
	TPTE2	ENST00000696858.2		c.-43-20872C>G		intron	N/A	ENSP00000512931.1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142024 AN: 152120 Hom.: 66600 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.936

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.933 AC: 142104 AN: 152238 Hom.: 66624 Cov.: 32 AF XY: 0.935 AC XY: 69577 AN XY: 74442

African (AFR) AF: 0.835 AC: 34643 AN: 41476

American (AMR) AF: 0.965 AC: 14769 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3255 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5190

South Asian (SAS) AF: 0.937 AC: 4528 AN: 4830

European-Finnish (FIN) AF: 0.983 AC: 10440 AN: 10618

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66143 AN: 68032

Other (OTH) AF: 0.937 AC: 1980 AN: 2114

Alfa AF: 0.947 Hom.: 8481

Bravo AF: 0.928

Asia WGS AF: 0.966 AC: 3360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2451078; hg19: chr13-20098289;