21-10561201-A-G

Position:

• chr21-10561201-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_199261.4(TPTE):​c.446+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00589 in 1,601,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (0 hom., cov: 60)
  • Exomes 𝑓: 0.0060 (0 hom.)
• Consequence: TPTE NM_199261.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 21-10561201-A-G is Benign according to our data. Variant chr21-10561201-A-G is described in ClinVar as [Benign]. Clinvar id is 791664.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPTE	NM_199261.4	c.446+10A>G		intron_variant		ENST00000618007.5	NP_954870.3
TPTE	NM_001290224.2	c.32+10A>G		intron_variant			NP_001277153.2
TPTE	NM_199259.4	c.392+10A>G		intron_variant			NP_954868.2
TPTE	NM_199260.4	c.332+10A>G		intron_variant			NP_954869.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE	ENST00000618007.5	c.446+10A>G		intron_variant		1	NM_199261.4	ENSP00000484403	P2

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 742 AN: 151998 Hom.: 0 Cov.: 60

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00520

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00854

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00481 AC: 1196 AN: 248594 Hom.: 0 AF XY: 0.00501 AC XY: 675 AN XY: 134720

Gnomad AFR exome AF: 0.00190

Gnomad AMR exome AF: 0.00152

Gnomad ASJ exome AF: 0.00251

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00298

Gnomad FIN exome AF: 0.00324

Gnomad NFE exome AF: 0.00794

Gnomad OTH exome AF: 0.00613

GnomAD4 exome AF: 0.00599 AC: 8685 AN: 1449672 Hom.: 0 Cov.: 32 AF XY: 0.00601 AC XY: 4339 AN XY: 721402

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00180

Gnomad4 ASJ exome AF: 0.00334

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00269

Gnomad4 FIN exome AF: 0.00343

Gnomad4 NFE exome AF: 0.00706

Gnomad4 OTH exome AF: 0.00456

GnomAD4 genome AF: 0.00488 AC: 743 AN: 152116 Hom.: 0 Cov.: 60 AF XY: 0.00477 AC XY: 355 AN XY: 74416

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00520

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00854

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00453 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201619647; hg19: chr21-10951256;