Variant Y-7070228-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BS2_Supporting

The NM_033284.2(TBL1Y):c.490G>A(p.Asp164Asn) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 4 hem., cov: 0)

Exomes 𝑓: 0.00034 ( 0 hom. 121 hem. )

Consequence

TBL1Y
NM_033284.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.84

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12749124).

BP6

Variant Y-7070228-G-A is Benign according to our data. Variant chrY-7070228-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3032479.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 4 YL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBL1Y	NM_033284.2 linkuse as main transcript	c.490G>A	p.Asp164Asn	missense_variant	9/19	ENST00000383032.6	NP_150600.1	Q9BQ87A0A024R189
TBL1Y	NM_134258.2 linkuse as main transcript	c.490G>A	p.Asp164Asn	missense_variant	8/18		NP_599020.1	Q9BQ87A0A024R189
TBL1Y	NM_134259.2 linkuse as main transcript	c.490G>A	p.Asp164Asn	missense_variant	8/18		NP_599021.1	Q9BQ87A0A024R189

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBL1Y	ENST00000383032.6 linkuse as main transcript	c.490G>A	p.Asp164Asn	missense_variant	9/19	1	NM_033284.2	ENSP00000372499.1	Q9BQ87
TBL1Y	ENST00000346432.3 linkuse as main transcript	c.490G>A	p.Asp164Asn	missense_variant	8/18	1		ENSP00000328879.4	Q9BQ87
TBL1Y	ENST00000355162.6 linkuse as main transcript	c.490G>A	p.Asp164Asn	missense_variant	8/18	1		ENSP00000347289.2	Q9BQ87

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

33575

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33575

show subpopulations

Gnomad AFR

AF:

0.000233

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

67645

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

67645

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.00

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:

0.000316

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000335

AC:

121

AN:

360973

Hom.:

Cov.:

AF XY:

0.000335

AC XY:

121

AN XY:

360973

show subpopulations

Gnomad4 AFR exome

AF:

0.000142

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:

0.000448

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000119

AC:

AN:

33575

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33575

show subpopulations

Gnomad4 AFR

AF:

0.000233

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:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000837

Hom.:

ExAC

AF:

0.000113

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TBL1Y-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 25, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.036

T;T;T

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.97

.;.;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

T;T;T

MutationAssessor

Benign

1.9

L;L;L

PROVEAN

Benign

-0.95

N;N;N

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.14

B;B;B

Vest4

0.26

MVP

0.26

GERP RS

2.7

Varity_R

0.15

gMVP

0.37

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