Y-7063916-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033284.2(TBL1Y):c.224G>T(p.Ser75Ile) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., 48 hem., cov: 0)

Exomes 𝑓: 0.0015 ( 0 hom. 556 hem. )

Consequence

TBL1Y
NM_033284.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.39

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008928269).

BP6

Variant Y-7063916-G-T is Benign according to our data. Variant chrY-7063916-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661885.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00153 (556/362880) while in subpopulation MID AF= 0.0221 (36/1629). AF 95% confidence interval is 0.0164. There are 0 homozygotes in gnomad4_exome. There are 556 alleles in male gnomad4_exome subpopulation. Median coverage is 15. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 48 YL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1Y	NM_033284.2 link	c.224G>T	p.Ser75Ile	missense_variant	Exon 8 of 19	ENST00000383032.6	NP_150600.1	Q9BQ87A0A024R189
TBL1Y	NM_134258.2 link	c.224G>T	p.Ser75Ile	missense_variant	Exon 7 of 18		NP_599020.1	Q9BQ87A0A024R189
TBL1Y	NM_134259.2 link	c.224G>T	p.Ser75Ile	missense_variant	Exon 7 of 18		NP_599021.1	Q9BQ87A0A024R189

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBL1Y	ENST00000383032.6 link	c.224G>T	p.Ser75Ile	missense_variant	Exon 8 of 19	1	NM_033284.2	ENSP00000372499.1	Q9BQ87
TBL1Y	ENST00000346432.3 link	c.224G>T	p.Ser75Ile	missense_variant	Exon 7 of 18	1		ENSP00000328879.4	Q9BQ87
TBL1Y	ENST00000355162.6 link	c.224G>T	p.Ser75Ile	missense_variant	Exon 7 of 18	1		ENSP00000347289.2	Q9BQ87

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

AN:

32785

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

AN XY:

32785

show subpopulations

Gnomad AFR

AF:

0.000360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00335

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000710

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00235

AC:

158

AN:

67143

Hom.:

AF XY:

0.00235

AC XY:

158

AN XY:

67143

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00503

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000875

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00153

AC:

556

AN:

362880

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

556

AN XY:

362880

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00536

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000881

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.00386

GnomAD4 genome

AF:

0.00146

AC:

AN:

32850

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

AN XY:

32850

show subpopulations

Gnomad4 AFR

AF:

0.000358

Gnomad4 AMR

AF:

0.00334

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000707

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00872

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00214

AC:

ExAC

AF:

0.00208

AC:

149

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TBL1Y: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

DANN

Benign

0.83

DEOGEN2

Benign

0.038

T;T;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.86

.;.;D

MetaRNN

Benign

0.0089

T;T;T

MutationAssessor

Benign

0.90

L;L;L

PROVEAN

Benign

-1.0

N;N;N

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.044

B;B;B

Vest4

0.14

MVP

0.11

GERP RS

2.3

Varity_R

0.22

gMVP

0.92

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