rs10439884

Positions:

• chr21-10540506-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199261.4(TPTE):​c.12-606C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 149,144 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.055 (0 hom., cov: 66)
• Consequence: TPTE NM_199261.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

Genes affected

TPTE (HGNC:12023): (transmembrane phosphatase with tensin homology) This gene encodes a PTEN-related tyrosine phosphatase which may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ENSG00000273840 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPTE	NM_199261.4	c.12-606C>T		intron_variant		ENST00000618007.5	NP_954870.3
TPTE	NM_199259.4	c.12-606C>T		intron_variant			NP_954868.2
TPTE	NM_199260.4	c.12-606C>T		intron_variant			NP_954869.2
TPTE	NM_001290224.2	c.-182+13094C>T		intron_variant			NP_001277153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE	ENST00000618007.5	c.12-606C>T		intron_variant		1	NM_199261.4	ENSP00000484403.1

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8163 AN: 149024 Hom.: 0 Cov.: 66

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0471

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0733

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.0663

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

GnomAD4 genome AF: 0.0547 AC: 8162 AN: 149144 Hom.: 0 Cov.: 66 AF XY: 0.0520 AC XY: 3793 AN XY: 72906

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.0445

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0469

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0861

Gnomad4 OTH AF: 0.0661

Alfa AF: 0.0864 Hom.: 93

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10439884; hg19: chr21-10971951;