Variant 14-55428899-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The ENST00000247219.6(TBPL2):c.768C>T(p.Leu256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,614,068 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 26 hom. )

Consequence

TBPL2
ENST00000247219.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.323

Variant links:

Genes affected

TBPL2 (HGNC:19841): (TATA-box binding protein like 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Predicted to be involved in DNA-templated transcription, initiation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TBPL2 links:

FBXO34 (HGNC:):

FBXO34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 14-55428899-G-A is Benign according to our data. Variant chr14-55428899-G-A is described in ClinVar as [Benign]. Clinvar id is 2644254.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.323 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00264 (3864/1461886) while in subpopulation MID AF= 0.0191 (110/5768). AF 95% confidence interval is 0.0162. There are 26 homozygotes in gnomad4_exome. There are 1925 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBPL2	NM_199047.3 linkuse as main transcript	c.768C>T	p.Leu256=	synonymous_variant	5/7	ENST00000247219.6	NP_950248.2
FBXO34	XR_007064022.1 linkuse as main transcript	n.2982+4815G>A		intron_variant, non_coding_transcript_variant
FBXO34	XR_007064023.1 linkuse as main transcript	n.2941-13928G>A		intron_variant, non_coding_transcript_variant
FBXO34	XR_007064024.1 linkuse as main transcript	n.2982+4815G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBPL2	ENST00000247219.6 linkuse as main transcript	c.768C>T	p.Leu256=	synonymous_variant	5/7	1	NM_199047.3	ENSP00000247219	P1

Frequencies

GnomAD3 genomes

AF:

0.00633

AC:

962

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00201

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00418

AC:

1050

AN:

251462

Hom.:

AF XY:

0.00393

AC XY:

534

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.00578

Gnomad ASJ exome

AF:

0.0212

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00279

Gnomad OTH exome

AF:

0.00847

GnomAD4 exome

AF:

0.00264

AC:

3864

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

1925

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.00711

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.00656

GnomAD4 genome

AF:

0.00633

AC:

964

AN:

152182

Hom.:

Cov.:

AF XY:

0.00640

AC XY:

476

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00201

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00420

Hom.:

Bravo

AF:

0.00717

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

TBPL2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

3.1

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over