Y-7070228-G-A

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

3
11

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]

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 rank MANE Protein UniProt
TBL1YNM_033284.2 linkc.490G>A p.Asp164Asn missense_variant Exon 9 of 19 ENST00000383032.6 NP_150600.1 Q9BQ87A0A024R189
TBL1YNM_134258.2 linkc.490G>A p.Asp164Asn missense_variant Exon 8 of 18 NP_599020.1 Q9BQ87A0A024R189
TBL1YNM_134259.2 linkc.490G>A p.Asp164Asn missense_variant Exon 8 of 18 NP_599021.1 Q9BQ87A0A024R189

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBL1YENST00000383032.6 linkc.490G>A p.Asp164Asn missense_variant Exon 9 of 19 1 NM_033284.2 ENSP00000372499.1 Q9BQ87
TBL1YENST00000346432.3 linkc.490G>A p.Asp164Asn missense_variant Exon 8 of 18 1 ENSP00000328879.4 Q9BQ87
TBL1YENST00000355162.6 linkc.490G>A p.Asp164Asn missense_variant Exon 8 of 18 1 ENSP00000347289.2 Q9BQ87

Frequencies

GnomAD3 genomes
AF:
0.000119
AC:
4
AN:
33575
Hom.:
0
Cov.:
0
AF XY:
0.000119
AC XY:
4
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:
11
AN:
67645
Hom.:
0
AF XY:
0.000163
AC XY:
11
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.:
0
Cov.:
0
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:
4
AN:
33575
Hom.:
0
Cov.:
0
AF XY:
0.000119
AC XY:
4
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.:
2
ExAC
AF:
0.000113
AC:
8

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

TBL1Y-related disorder Benign:1
Jan 25, 2023
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
22
DANN
Uncertain
0.97
DEOGEN2
Benign
0.036
T;T;T
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.97
.;.;D
M_CAP
Benign
0.015
T
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.

Other links and lift over

dbSNP: rs779411676; hg19: chrY-6938269; API