rs868176098

Variant names:

• chr6-46688180-G-A
• NM_001010870.3:c.52G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-46688180-G-A
• chr6-46688180-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001010870.3(TDRD6):​c.52G>A​(p.Val18Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V18L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TDRD6 NM_001010870.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD6	NM_001010870.3	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 4	ENST00000316081.11	NP_001010870.1
TDRD6	NM_001168359.2	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 3		NP_001161831.1
TDRD6	NR_144468.2	n.1372+6541G>A		intron_variant	Intron 1 of 3
TDRD6-AS1	NR_134643.1	n.-15C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD6	ENST00000316081.11	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 4	1	NM_001010870.3	ENSP00000346065.5
TDRD6	ENST00000544460.5	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 3	2		ENSP00000443299.1
TDRD6-AS1	ENST00000434329.2	n.-15C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398810 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 692274

Gnomad4 AFR exome AF: 0.0000320

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.85	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	.;D
Vest4		0.56
MutPred		0.63		Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);
MVP		0.38
MPC		0.23
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.17
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-46655917;