21-10561044-T-C

Position:

• chr21-10561044-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_199261.4(TPTE):​c.299T>C​(p.Phe100Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 60)
  • Exomes 𝑓: 0.000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPTE NM_199261.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13386557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPTE	NM_199261.4	c.299T>C	p.Phe100Ser	missense_variant	10/24	ENST00000618007.5	NP_954870.3
TPTE	NM_199259.4	c.245T>C	p.Phe82Ser	missense_variant	9/23		NP_954868.2
TPTE	NM_199260.4	c.185T>C	p.Phe62Ser	missense_variant	8/22		NP_954869.2
TPTE	NM_001290224.2	c.-116T>C		5_prime_UTR_variant	5/19		NP_001277153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE	ENST00000618007.5	c.299T>C	p.Phe100Ser	missense_variant	10/24	1	NM_199261.4	ENSP00000484403	P2

Frequencies

GnomAD3 genomes Cov.: 60

GnomAD3 exomes AF: 0.0000679 AC: 17 AN: 250226 Hom.: 0 AF XY: 0.0000370 AC XY: 5 AN XY: 135306

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000158 AC: 23 AN: 1459382 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 725968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000493

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 60

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.299T>C (p.F100S) alteration is located in exon 10 (coding exon 7) of the TPTE gene. This alteration results from a T to C substitution at nucleotide position 299, causing the phenylalanine (F) at amino acid position 100 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.78
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.28	.;T;T;.
LIST_S2	Benign	0.55	T;T;T;T
MetaRNN	Benign	0.13	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Vest4		0.30
gMVP		0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs757957068; hg19: chr21-10951413;