1-151776480-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_001083965.2(TDRKH):c.1003A>T(p.Lys335Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TDRKH NM_001083965.2 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.52

Genes affected

TDRKH (HGNC:11713): (tudor and KH domain containing) Predicted to enable RNA binding activity. Predicted to be involved in fertilization; gamete generation; and piRNA metabolic process. Predicted to be located in mitochondrion; pi-body; and piP-body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001083965.2 Downstream stopcodon found after 31 codons.
• PP5: Variant 1-151776480-T-A is Pathogenic according to our data. Variant chr1-151776480-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 1328954.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-151776480-T-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRKH	NM_001083965.2	c.1003A>T	p.Lys335Ter	stop_gained	7/13	ENST00000368824.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRKH	ENST00000368824.8	c.1003A>T	p.Lys335Ter	stop_gained	7/13	1	NM_001083965.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Azoospermia Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Genetics of Infertility and Preimplantation Genetic Diagnosis, Centre Hospitalier Universitaire Grenoble Alpes

Dec 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
Cadd	Pathogenic	38
Dann	Uncertain	1.0
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.92	D
MutationTaster	Benign	1.0	A;A;A;A;A;A;A
Vest4		0.35
GERP RS		5.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-151748956;