chr21-10602053-CAT-C

Position:

• chr21-10602053-CAT-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_199261.4(TPTE):​c.1357-3_1357-2del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 151,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 81)
  • Exomes 𝑓: 0.0046 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPTE NM_199261.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.818

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPTE	NM_199261.4	c.1357-3_1357-2del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000618007.5	NP_954870.3
TPTE	NM_001290224.2	c.943-3_943-2del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001277153.2
TPTE	NM_199259.4	c.1303-3_1303-2del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_954868.2
TPTE	NM_199260.4	c.1243-3_1243-2del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_954869.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE	ENST00000618007.5	c.1357-3_1357-2del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_199261.4	ENSP00000484403	P2
TPTE	ENST00000427445.6	c.1243-3_1243-2del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000482488	A2
TPTE	ENST00000612746.1	c.943-3_943-2del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000483087
TPTE	ENST00000622113.4	c.1303-3_1303-2del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000482040	A2

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 413 AN: 151544 Hom.: 0 Cov.: 81

Gnomad AFR AF: 0.000918

Gnomad AMI AF: 0.0218

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00480

Gnomad OTH AF: 0.00336

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00457 AC: 6623 AN: 1449832 Hom.: 0 AF XY: 0.00440 AC XY: 3174 AN XY: 721566

Gnomad4 AFR exome AF: 0.000778

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00167

Gnomad4 NFE exome AF: 0.00557

Gnomad4 OTH exome AF: 0.00497

GnomAD4 genome AF: 0.00272 AC: 413 AN: 151662 Hom.: 0 Cov.: 81 AF XY: 0.00242 AC XY: 180 AN XY: 74232

Gnomad4 AFR AF: 0.000915

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00480

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00506 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism spectrum disorder;C2243051:Macrocephaly Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Abrahams Lab, Albert Einstein College of Medicine

Dec 22, 2014

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149363218; hg19: chr21-10910404;