Y-6950250-C-T

Position:

• chrY-6950250-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000383032.6(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 ENST00000383032.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TBL1Y	NM_033284.2	c.-265-27963C>T		intron_variant		ENST00000383032.6	NP_150600.1
TBL1Y	NM_134258.2	c.-235+38078C>T		intron_variant			NP_599020.1
TBL1Y	NM_134259.2	c.-170-27963C>T		intron_variant			NP_599021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBL1Y	ENST00000383032.6	c.-265-27963C>T		intron_variant		1	NM_033284.2	ENSP00000372499	P1
TBL1Y	ENST00000346432.3	c.-170-27963C>T		intron_variant		1		ENSP00000328879	P1
TBL1Y	ENST00000355162.6	c.-235+38078C>T		intron_variant		1		ENSP00000347289	P1

Frequencies

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

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

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00202

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.0366 Hom.: 696

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

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

Other links and lift over

dbSNP: rs768983; hg19: chrY-6818291;