ENST00000422284.7:n.270+1548T>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000422284.7(TDRD6-AS1):​n.270+1548T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD6-AS1	NR_134642.1	n.234+1548T>G		intron_variant	Intron 1 of 1
TDRD6-AS1	NR_134643.1	n.232+1882T>G		intron_variant	Intron 1 of 1
TDRD6-AS1	NR_134644.1	n.159+1623T>G		intron_variant	Intron 1 of 1
TDRD6	NR_144468.2	n.1372+4413A>C		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>G		intron_variant	Intron 1 of 1	2
TDRD6-AS1	ENST00000434329.3	n.362+1882T>G		intron_variant	Intron 1 of 1	3
TDRD6-AS1	ENST00000571590.6	n.199+1623T>G		intron_variant	Intron 1 of 1	3
TDRD6-AS1	ENST00000734840.1	n.401+1398T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.59
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;