chrY-7064105-G-A

Variant names:

• chrY-7064105-G-A
• rs377026718
• NM_033284.2:c.413G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BS2_Supporting

The NM_033284.2(TBL1Y):​c.413G>A​(p.Arg138Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., 11 hem., cov: 0)
  • Exomes 𝑓: 0.00035 (0 hom. 127 hem.)
• Consequence: TBL1Y NM_033284.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.32
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014740616).
• BP6: Variant Y-7064105-G-A is Benign according to our data. Variant chrY-7064105-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3033002.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 11 YL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033284.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1Y	NM_033284.2	MANE Select	c.413G>A	p.Arg138Gln	missense	Exon 8 of 19	NP_150600.1	Q9BQ87
	TBL1Y	NM_134258.2		c.413G>A	p.Arg138Gln	missense	Exon 7 of 18	NP_599020.1	Q9BQ87
	TBL1Y	NM_134259.2		c.413G>A	p.Arg138Gln	missense	Exon 7 of 18	NP_599021.1	Q9BQ87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1Y	ENST00000383032.6	TSL:1 MANE Select	c.413G>A	p.Arg138Gln	missense	Exon 8 of 19	ENSP00000372499.1	Q9BQ87
	TBL1Y	ENST00000346432.3	TSL:1	c.413G>A	p.Arg138Gln	missense	Exon 7 of 18	ENSP00000328879.4	Q9BQ87
	TBL1Y	ENST00000355162.6	TSL:1	c.413G>A	p.Arg138Gln	missense	Exon 7 of 18	ENSP00000347289.2	Q9BQ87

Frequencies

GnomAD3 genomes AF: 0.000327 AC: 11 AN: 33676 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000270

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00239

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000270 AC: 18 AN: 66764 AF XY: 0.000270

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000665

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000324

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000350 AC: 127 AN: 362937 Hom.: 0 Cov.: 1 AF XY: 0.000350 AC XY: 127 AN XY: 362937

African (AFR) AF: 0.000141 AC: 1 AN: 7074

American (AMR) AF: 0.000105 AC: 1 AN: 9513

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6742

East Asian (EAS) AF: 0.000633 AC: 6 AN: 9483

South Asian (SAS) AF: 0.000535 AC: 17 AN: 31779

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12873

Middle Eastern (MID) AF: 0.00184 AC: 3 AN: 1630

European-Non Finnish (NFE) AF: 0.000326 AC: 88 AN: 269576

Other (OTH) AF: 0.000771 AC: 11 AN: 14267

GnomAD4 genome AF: 0.000326 AC: 11 AN: 33740 Hom.: 0 Cov.: 0 AF XY: 0.000326 AC XY: 11 AN XY: 33740

African (AFR) AF: 0.000231 AC: 2 AN: 8646

American (AMR) AF: 0.000269 AC: 1 AN: 3713

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 773

East Asian (EAS) AF: 0.00239 AC: 3 AN: 1254

South Asian (SAS) AF: 0.00 AC: 0 AN: 1466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 73

European-Non Finnish (NFE) AF: 0.000367 AC: 5 AN: 13625

Other (OTH) AF: 0.00 AC: 0 AN: 481

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TBL1Y-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
PhyloP100		5.3
Varity_R		0.064
gMVP		0.40
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs377026718; hg19: chrY-6932146;