Y-7064105-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_033284.2(TBL1Y):​c.413G>T​(p.Arg138Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R138Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., 2 hem., cov: 0)
  • Exomes 𝑓: 0.000022 (0 hom. 8 hem.)
  • Failed GnomAD Quality Control
• Consequence: TBL1Y NM_033284.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15033245).
• BS2: High Hemizygotes in GnomAd4 at 2 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>T	p.Arg138Leu	missense	Exon 8 of 19	NP_150600.1	Q9BQ87
	TBL1Y	NM_134258.2		c.413G>T	p.Arg138Leu	missense	Exon 7 of 18	NP_599020.1	Q9BQ87
	TBL1Y	NM_134259.2		c.413G>T	p.Arg138Leu	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>T	p.Arg138Leu	missense	Exon 8 of 19	ENSP00000372499.1	Q9BQ87
	TBL1Y	ENST00000346432.3	TSL:1	c.413G>T	p.Arg138Leu	missense	Exon 7 of 18	ENSP00000328879.4	Q9BQ87
	TBL1Y	ENST00000355162.6	TSL:1	c.413G>T	p.Arg138Leu	missense	Exon 7 of 18	ENSP00000347289.2	Q9BQ87

Frequencies

GnomAD3 genomes AF: 0.0000594 AC: 2 AN: 33676 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000150 AC: 1 AN: 66764 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000324

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000220 AC: 8 AN: 362937 Hom.: 0 Cov.: 1 AF XY: 0.0000220 AC XY: 8 AN XY: 362937

African (AFR) AF: 0.00 AC: 0 AN: 7074

American (AMR) AF: 0.00 AC: 0 AN: 9513

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 9483

South Asian (SAS) AF: 0.00 AC: 0 AN: 31779

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1630

European-Non Finnish (NFE) AF: 0.0000297 AC: 8 AN: 269576

Other (OTH) AF: 0.00 AC: 0 AN: 14267

GnomAD4 genome AF: 0.0000594 AC: 2 AN: 33676 Hom.: 0 Cov.: 0 AF XY: 0.0000594 AC XY: 2 AN XY: 33676

African (AFR) AF: 0.00 AC: 0 AN: 8593

American (AMR) AF: 0.00 AC: 0 AN: 3706

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 1255

South Asian (SAS) AF: 0.00 AC: 0 AN: 1462

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.000147 AC: 2 AN: 13626

Other (OTH) AF: 0.00 AC: 0 AN: 478

ExAC AF: 0.0000287 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.047	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.15	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.3
PROVEAN	Benign	-1.5	N
Sift	Benign	0.26	T
Sift4G	Benign	0.27	T
Polyphen		0.010	B
Vest4		0.27
MVP		0.12
GERP RS		2.3
Varity_R		0.099
gMVP		0.45
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: rs377026718; hg19: chrY-6932146;