chrY-6950250-C-T

Variant names:

• chrY-6950250-C-T
• rs768983
• NM_033284.2:c.-265-27963C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033284.2(TBL1Y):​c.-265-27963C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (0 hom., 5215 hem., cov: 0)
• Consequence: TBL1Y NM_033284.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• deafness, Y-linked 2

  Inheritance: YL Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1Y	NM_033284.2	c.-265-27963C>T		intron_variant	Intron 2 of 18	ENST00000383032.6	NP_150600.1
TBL1Y	NM_134258.2	c.-235+38078C>T		intron_variant	Intron 2 of 17		NP_599020.1
TBL1Y	NM_134259.2	c.-170-27963C>T		intron_variant	Intron 2 of 17		NP_599021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1Y	ENST00000383032.6	c.-265-27963C>T		intron_variant	Intron 2 of 18	1	NM_033284.2	ENSP00000372499.1
TBL1Y	ENST00000346432.3	c.-170-27963C>T		intron_variant	Intron 2 of 17	1		ENSP00000328879.4
TBL1Y	ENST00000355162.6	c.-235+38078C>T		intron_variant	Intron 2 of 17	1		ENSP00000347289.2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 5183 AN: 33111 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00203

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0278

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.0864

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 5215 AN: 33172 Hom.: 0 Cov.: 0 AF XY: 0.157 AC XY: 5215 AN XY: 33172

African (AFR) AF: 0.599 AC: 5005 AN: 8350

American (AMR) AF: 0.0374 AC: 136 AN: 3639

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 764

East Asian (EAS) AF: 0.00 AC: 0 AN: 1272

South Asian (SAS) AF: 0.00202 AC: 3 AN: 1483

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3425

Middle Eastern (MID) AF: 0.0286 AC: 2 AN: 70

European-Non Finnish (NFE) AF: 0.00215 AC: 29 AN: 13489

Other (OTH) AF: 0.0858 AC: 40 AN: 466

Alfa AF: 0.107 Hom.: 4560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.50
PhyloP100		0.91

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

Other links and lift over

dbSNP: rs768983; hg19: chrY-6818291;