chr6-46702199-C-A

Variant names:

• chr6-46702199-C-A
• rs12528857
• NM_001010870.3:c.*312C>A

Variant summary

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

The NM_001010870.3(TDRD6):​c.*312C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 215,578 control chromosomes in the GnomAD database, including 4,264 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 0.17 (2747 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1517 hom.)
• Consequence: TDRD6 NM_001010870.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 17 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD6	NM_001010870.3	c.*312C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000316081.11	NP_001010870.1
TDRD6	NR_144468.2	n.1929C>A		non_coding_transcript_exon_variant	Exon 4 of 4
TDRD6	NM_001168359.2	c.*312C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001161831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD6	ENST00000316081.11	c.*312C>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_001010870.3	ENSP00000346065.5
TDRD6	ENST00000544460.5	c.*312C>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000443299.1
TDRD6	ENST00000450697.1	c.*298C>A		downstream_gene_variant		5		ENSP00000397165.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25821 AN: 151878 Hom.: 2745 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.215 AC: 13669 AN: 63582 Hom.: 1517 Cov.: 0 AF XY: 0.218 AC XY: 7183 AN XY: 32996

African (AFR) AF: 0.0568 AC: 130 AN: 2290

American (AMR) AF: 0.151 AC: 318 AN: 2104

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 800 AN: 2558

East Asian (EAS) AF: 0.112 AC: 607 AN: 5396

South Asian (SAS) AF: 0.271 AC: 217 AN: 802

European-Finnish (FIN) AF: 0.221 AC: 769 AN: 3474

Middle Eastern (MID) AF: 0.299 AC: 101 AN: 338

European-Non Finnish (NFE) AF: 0.232 AC: 9802 AN: 42260

Other (OTH) AF: 0.212 AC: 925 AN: 4360

GnomAD4 genome AF: 0.170 AC: 25822 AN: 151996 Hom.: 2747 Cov.: 32 AF XY: 0.171 AC XY: 12668 AN XY: 74298

African (AFR) AF: 0.0503 AC: 2088 AN: 41512

American (AMR) AF: 0.146 AC: 2233 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1001 AN: 3464

East Asian (EAS) AF: 0.133 AC: 686 AN: 5174

South Asian (SAS) AF: 0.280 AC: 1348 AN: 4816

European-Finnish (FIN) AF: 0.228 AC: 2400 AN: 10538

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15403 AN: 67910

Other (OTH) AF: 0.188 AC: 396 AN: 2106

Alfa AF: 0.218 Hom.: 2501

Bravo AF: 0.153

Asia WGS AF: 0.171 AC: 596 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.64
DANN	Benign	0.49
PhyloP100		-1.1
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: rs12528857; hg19: chr6-46669936;