rs10439884

Variant names:

• chr21-10540506-C-T
• rs10439884
• NM_199261.4:c.12-606C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

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
• Publications: 7 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the NFE (0.0842) population. However there is too low homozygotes in high coverage region: (expected more than 111, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPTE	NM_199261.4	c.12-606C>T		intron_variant	Intron 4 of 23	ENST00000618007.5	NP_954870.3
TPTE	NM_199259.4	c.12-606C>T		intron_variant	Intron 4 of 22		NP_954868.2
TPTE	NM_199260.4	c.12-606C>T		intron_variant	Intron 4 of 21		NP_954869.2
TPTE	NM_001290224.2	c.-182+13094C>T		intron_variant	Intron 3 of 18		NP_001277153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPTE	ENST00000618007.5	c.12-606C>T		intron_variant	Intron 4 of 23	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

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

African (AFR) AF: 0.0144 AC: 594 AN: 41312

American (AMR) AF: 0.0445 AC: 666 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 281 AN: 3360

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0469 AC: 222 AN: 4730

European-Finnish (FIN) AF: 0.0481 AC: 502 AN: 10428

Middle Eastern (MID) AF: 0.0719 AC: 20 AN: 278

European-Non Finnish (NFE) AF: 0.0861 AC: 5677 AN: 65936

Other (OTH) AF: 0.0661 AC: 135 AN: 2042

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0779 Hom.: 360

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
PhyloP100		-0.96

Splicing

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

Other links and lift over

dbSNP: rs10439884; hg19: chr21-10971951;