6-46699606-C-T

Variant names:

• chr6-46699606-C-T
• rs974670
• NM_001010870.3:c.6261+1519C>T

Variant summary

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

The NM_001010870.3(TDRD6):​c.6261+1519C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,884 control chromosomes in the GnomAD database, including 8,740 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 0.30 (8740 hom., cov: 32)
• Consequence: TDRD6 NM_001010870.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 15 publications found

Genes affected

TDRD6 (HGNC:21339): (tudor domain containing 6) This gene encodes a tudor domain-containing protein and component of the chromatoid body, a type of ribonucleoprotein granule present in male germ cells. Studies in rodents have demonstrated a role for the encoded protein in spermiogenesis and the nonsense mediated decay (NMD) pathway. This protein is a major autoantigen in human patients with autoimmune polyendocrine syndrome type 1 (APS1). [provided by RefSeq, Oct 2016]

TDRD6 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
• schizophrenia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• oligospermia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010870.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD6	NM_001010870.3	MANE Select	c.6261+1519C>T		intron	N/A	NP_001010870.1
	TDRD6	NM_001168359.2		c.6172-2252C>T		intron	N/A	NP_001161831.1
	TDRD6	NR_144468.2		n.1587+1519C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD6	ENST00000316081.11	TSL:1 MANE Select	c.6261+1519C>T		intron	N/A	ENSP00000346065.5
	TDRD6	ENST00000544460.5	TSL:2	c.6172-2252C>T		intron	N/A	ENSP00000443299.1
	TDRD6	ENST00000450697.1	TSL:5	c.418-1393C>T		intron	N/A	ENSP00000397165.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45990 AN: 151766 Hom.: 8736 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.303 AC: 46000 AN: 151884 Hom.: 8740 Cov.: 32 AF XY: 0.303 AC XY: 22521 AN XY: 74206

African (AFR) AF: 0.0789 AC: 3269 AN: 41440

American (AMR) AF: 0.329 AC: 5010 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1091 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2909 AN: 5170

South Asian (SAS) AF: 0.206 AC: 991 AN: 4810

European-Finnish (FIN) AF: 0.389 AC: 4080 AN: 10486

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27706 AN: 67948

Other (OTH) AF: 0.295 AC: 622 AN: 2112

Alfa AF: 0.359 Hom.: 5636

Bravo AF: 0.291

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.26
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs974670; hg19: chr6-46667343;