Genetic Variant TBL1Y:c.457+1G>T (chrY-7064150-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_033284.2(TBL1Y):c.457+1G>T variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000030 ( 0 hom., 1 hem., cov: 0)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

TBL1Y
NM_033284.2 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.23

Variant links:

Genes affected

TBL1Y (HGNC:18502): (transducin beta like 1 Y-linked) The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This gene is highly similar to TBL1X gene in nucleotide sequence and protein sequence, but the TBL1X gene is located on chromosome X and this gene is on chromosome Y. This gene has three alternatively spliced transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

TBL1Y links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TBL1Y	NM_033284.2 link	c.457+1G>T	splice_donor_variant, intron_variant	Intron 8 of 18	ENST00000383032.6	NP_150600.1	Q9BQ87A0A024R189
TBL1Y	NM_134258.2 link	c.457+1G>T	splice_donor_variant, intron_variant	Intron 7 of 17		NP_599020.1	Q9BQ87A0A024R189
TBL1Y	NM_134259.2 link	c.457+1G>T	splice_donor_variant, intron_variant	Intron 7 of 17		NP_599021.1	Q9BQ87A0A024R189

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBL1Y	ENST00000383032.6 link	c.457+1G>T	splice_donor_variant, intron_variant	Intron 8 of 18	1	NM_033284.2	ENSP00000372499.1	Q9BQ87
TBL1Y	ENST00000346432.3 link	c.457+1G>T	splice_donor_variant, intron_variant	Intron 7 of 17	1		ENSP00000328879.4	Q9BQ87
TBL1Y	ENST00000355162.6 link	c.457+1G>T	splice_donor_variant, intron_variant	Intron 7 of 17	1		ENSP00000347289.2	Q9BQ87

Frequencies

GnomAD3 genomes

AF:

0.0000297

AC:

AN:

33693

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33693

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000276

AC:

AN:

362794

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000701

GnomAD4 genome

AF:

0.0000297

AC:

AN:

33693

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33693

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.78

FATHMM_MKL

Pathogenic

0.98

GERP RS

2.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.74

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.99

Position offset: -1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over