rs3811413

Positions:

• chr1-151776353-G-A

Variant summary

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

The NM_001083965.2(TDRKH):​c.1045-85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,593,974 control chromosomes in the GnomAD database, including 7,246 homozygotes. 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 0.039 (722 hom., cov: 32)
  • Exomes 𝑓: 0.035 (6524 hom.)
• Consequence: TDRKH NM_001083965.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRKH	NM_001083965.2	c.1045-85C>T		intron_variant		ENST00000368824.8	NP_001077434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRKH	ENST00000368824.8	c.1045-85C>T		intron_variant		1	NM_001083965.2	ENSP00000357815.3

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5969 AN: 152140 Hom.: 726 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00465

Gnomad OTH AF: 0.0482

GnomAD4 exome AF: 0.0347 AC: 49973 AN: 1441716 Hom.: 6524 Cov.: 32 AF XY: 0.0389 AC XY: 27836 AN XY: 714988

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.00264

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.000492

Gnomad4 NFE exome AF: 0.00365

Gnomad4 OTH exome AF: 0.0468

GnomAD4 genome AF: 0.0391 AC: 5955 AN: 152258 Hom.: 722 Cov.: 32 AF XY: 0.0457 AC XY: 3401 AN XY: 74456

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00465

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0199 Hom.: 266

Bravo AF: 0.0499

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.39

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: rs3811413; hg19: chr1-151748829; COSMIC: COSV64316102; COSMIC: COSV64316102;