6-46686052-A-G

Variant names:

• chr6-46686052-A-G
• rs9472819
• ENST00000422284.7:n.270+1548T>C

Variant summary

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

The ENST00000422284.7(TDRD6-AS1):​n.270+1548T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,074 control chromosomes in the GnomAD database, including 55,741 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 0.85 (55741 hom., cov: 30)
• Consequence: TDRD6-AS1 ENST00000422284.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 10 publications found

Genes affected

TDRD6-AS1 (HGNC:56119): (TDRD6 and SLC25A27 antisense RNA 1)

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD6-AS1	NR_134642.1	n.234+1548T>C		intron_variant	Intron 1 of 1
TDRD6-AS1	NR_134643.1	n.232+1882T>C		intron_variant	Intron 1 of 1
TDRD6-AS1	NR_134644.1	n.159+1623T>C		intron_variant	Intron 1 of 1
TDRD6	NR_144468.2	n.1372+4413A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD6-AS1	ENST00000422284.7	n.270+1548T>C		intron_variant	Intron 1 of 1	2
TDRD6-AS1	ENST00000434329.3	n.362+1882T>C		intron_variant	Intron 1 of 1	3
TDRD6-AS1	ENST00000571590.6	n.199+1623T>C		intron_variant	Intron 1 of 1	3
TDRD6-AS1	ENST00000734840.1	n.401+1398T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129615 AN: 151954 Hom.: 55684 Cov.: 30

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.853 AC: 129732 AN: 152074 Hom.: 55741 Cov.: 30 AF XY: 0.853 AC XY: 63384 AN XY: 74316

African (AFR) AF: 0.954 AC: 39580 AN: 41490

American (AMR) AF: 0.853 AC: 13048 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2856 AN: 3470

East Asian (EAS) AF: 0.886 AC: 4577 AN: 5164

South Asian (SAS) AF: 0.892 AC: 4292 AN: 4812

European-Finnish (FIN) AF: 0.763 AC: 8051 AN: 10556

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54741 AN: 67968

Other (OTH) AF: 0.841 AC: 1780 AN: 2116

Alfa AF: 0.815 Hom.: 74163

Bravo AF: 0.857

Asia WGS AF: 0.901 AC: 3132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.49
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs9472819; hg19: chr6-46653789;