rs17316227

Variant names:

• chrY-7038033-A-G
• rs17316227
• NM_033284.2:c.59-4947A>G

Variant summary

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

The NM_033284.2(TBL1Y):​c.59-4947A>G 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 0.059 (0 hom., 2010 hem., cov: 0)
• Consequence: TBL1Y NM_033284.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1Y	NM_033284.2	c.59-4947A>G		intron_variant	Intron 6 of 18	ENST00000383032.6	NP_150600.1
TBL1Y	NM_134258.2	c.59-4947A>G		intron_variant	Intron 5 of 17		NP_599020.1
TBL1Y	NM_134259.2	c.59-4947A>G		intron_variant	Intron 5 of 17		NP_599021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1Y	ENST00000383032.6	c.59-4947A>G		intron_variant	Intron 6 of 18	1	NM_033284.2	ENSP00000372499.1
TBL1Y	ENST00000346432.3	c.59-4947A>G		intron_variant	Intron 5 of 17	1		ENSP00000328879.4
TBL1Y	ENST00000355162.6	c.59-4947A>G		intron_variant	Intron 5 of 17	1		ENSP00000347289.2

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 2011 AN: 33923 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00932

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.00611

Gnomad ASJ AF: 0.0765

Gnomad EAS AF: 0.00236

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0282

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0418

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

GnomAD4 genome AF: 0.0591 AC: 2010 AN: 33987 Hom.: 0 Cov.: 0 AF XY: 0.0591 AC XY: 2010 AN XY: 33987

African (AFR) AF: 0.00926 AC: 81 AN: 8743

American (AMR) AF: 0.00610 AC: 23 AN: 3770

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 59 AN: 771

East Asian (EAS) AF: 0.00237 AC: 3 AN: 1268

South Asian (SAS) AF: 0.305 AC: 454 AN: 1487

European-Finnish (FIN) AF: 0.0350 AC: 123 AN: 3515

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

European-Non Finnish (NFE) AF: 0.0907 AC: 1240 AN: 13665

Other (OTH) AF: 0.0415 AC: 20 AN: 482

Alfa AF: 0.0970 Hom.: 4452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.31
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism

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: rs17316227; hg19: chrY-6906074;