Variant rs200332530 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_033284.2(TBL1Y):c.224G>C(p.Ser75Thr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000031 ( 0 hom., 1 hem., cov: 0)

Exomes 𝑓: 0.000014 ( 0 hom. 5 hem. )

Consequence

TBL1Y
NM_033284.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16897178).

BS2

High Hemizygotes in GnomAdExome4 at 5 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
TBL1Y	NM_033284.2 link	c.224G>C	p.Ser75Thr	missense_variant	Exon 8 of 19	ENST00000383032.6	NP_150600.1	Q9BQ87A0A024R189
TBL1Y	NM_134258.2 link	c.224G>C	p.Ser75Thr	missense_variant	Exon 7 of 18		NP_599020.1	Q9BQ87A0A024R189
TBL1Y	NM_134259.2 link	c.224G>C	p.Ser75Thr	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>C	p.Ser75Thr	missense_variant	Exon 8 of 19	1	NM_033284.2	ENSP00000372499.1	Q9BQ87
TBL1Y	ENST00000346432.3 link	c.224G>C	p.Ser75Thr	missense_variant	Exon 7 of 18	1		ENSP00000328879.4	Q9BQ87
TBL1Y	ENST00000355162.6 link	c.224G>C	p.Ser75Thr	missense_variant	Exon 7 of 18	1		ENSP00000347289.2	Q9BQ87

Frequencies

GnomAD3 genomes

AF:

0.0000305

AC:

AN:

32785

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32785

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:

0.0000745

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000298

AC:

AN:

67143

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67143

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000642

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

362880

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362880

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:

0.0000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000305

AC:

AN:

32785

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32785

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:

0.0000745

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000279

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.77

CADD

Uncertain

DANN

Benign

0.81

DEOGEN2

Benign

0.030

T;T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

.;.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.17

T;T;T

MutationAssessor

Benign

0.090

N;N;N

PROVEAN

Benign

-0.88

N;N;N

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.60

T;T;T

Polyphen

0.037

B;B;B

Vest4

0.27

MVP

0.055

GERP RS

2.3

Varity_R

0.30

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over