Y-7063898-A-T

Position:

chrY-7063898-A-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The ENST00000383032.6(TBL1Y):c.206A>T(p.Asp69Val) variant causes a missense, splice region change. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., 19 hem., cov: 0)

Exomes 𝑓: 0.00043 ( 0 hom. 157 hem. )

Failed GnomAD Quality Control

Consequence

TBL1Y
ENST00000383032.6 missense, splice_region

Scores

Splicing: ADA: 0.0005621

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.04

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 -1 ACMG points.

PP5

Variant Y-7063898-A-T is Pathogenic according to our data. Variant chrY-7063898-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 625467.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrY-7063898-A-T is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.18645236). . Strength limited to SUPPORTING due to the PP5.

BS2

High Hemizygotes in GnomAd4 at 19 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
TBL1Y	NM_033284.2 linkuse as main transcript	c.206A>T	p.Asp69Val	missense_variant, splice_region_variant	8/19	ENST00000383032.6	NP_150600.1
TBL1Y	NM_134258.2 linkuse as main transcript	c.206A>T	p.Asp69Val	missense_variant, splice_region_variant	7/18		NP_599020.1
TBL1Y	NM_134259.2 linkuse as main transcript	c.206A>T	p.Asp69Val	missense_variant, splice_region_variant	7/18		NP_599021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TBL1Y	ENST00000383032.6 linkuse as main transcript	c.206A>T	p.Asp69Val	missense_variant, splice_region_variant	8/19	1	NM_033284.2	ENSP00000372499	P1
TBL1Y	ENST00000346432.3 linkuse as main transcript	c.206A>T	p.Asp69Val	missense_variant, splice_region_variant	7/18	1		ENSP00000328879	P1
TBL1Y	ENST00000355162.6 linkuse as main transcript	c.206A>T	p.Asp69Val	missense_variant, splice_region_variant	7/18	1		ENSP00000347289	P1

Frequencies

GnomAD3 genomes

AF:

0.000584

AC:

AN:

32547

Hom.:

Cov.:

AF XY:

0.000584

AC XY:

AN XY:

32547

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000562

Gnomad ASJ

AF:

0.00524

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000899

Gnomad OTH

AF:

0.00221

GnomAD3 exomes

AF:

0.000671

AC:

AN:

67052

Hom.:

AF XY:

0.000671

AC XY:

AN XY:

67052

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000699

Gnomad ASJ exome

AF:

0.00582

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000876

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000708

Gnomad OTH exome

AF:

0.000629

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000433

AC:

157

AN:

362891

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

157

AN XY:

362891

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000841

Gnomad4 ASJ exome

AF:

0.00564

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000629

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000293

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.000584

AC:

AN:

32547

Hom.:

Cov.:

AF XY:

0.000584

AC XY:

AN XY:

32547

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000562

Gnomad4 ASJ

AF:

0.00524

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000899

Gnomad4 OTH

AF:

0.00221

Alfa

AF:

0.00167

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00160

AC:

ExAC

AF:

0.000476

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Deafness, Y-linked 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

.;.;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.19

T;T;T

MutationAssessor

Uncertain

2.9

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Pathogenic

-6.4

D;D;D

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.93

P;P;P

Vest4

0.62

MVP

0.16

GERP RS

2.3

Varity_R

0.68

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00056

dbscSNV1_RF

Benign

0.0060

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