rs1438599408

Variant names:

• chr6-46688214-C-A
• NM_001010870.3:c.86C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-46688214-C-A
• chr6-46688214-C-G
• chr6-46688214-C-T

Variant summary

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

The NM_001010870.3(TDRD6):​c.86C>A​(p.Pro29Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,388,948 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. P29L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TDRD6 NM_001010870.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08

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.86C>A	p.Pro29Gln	missense_variant	Exon 1 of 4	ENST00000316081.11	NP_001010870.1
TDRD6	NM_001168359.2	c.86C>A	p.Pro29Gln	missense_variant	Exon 1 of 3		NP_001161831.1
TDRD6	NR_144468.2	n.1372+6575C>A		intron_variant	Intron 1 of 3
TDRD6-AS1	NR_134643.1	n.-49G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD6	ENST00000316081.11	c.86C>A	p.Pro29Gln	missense_variant	Exon 1 of 4	1	NM_001010870.3	ENSP00000346065.5
TDRD6	ENST00000544460.5	c.86C>A	p.Pro29Gln	missense_variant	Exon 1 of 3	2		ENSP00000443299.1
TDRD6-AS1	ENST00000434329.2	n.-49G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388948 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 686764

Gnomad4 AFR exome AF: 0.00

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: 0.0000271

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	0.84
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.22
Sift	Benign	0.034	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		1.0	.;D
Vest4		0.64
MutPred		0.60		Gain of catalytic residue at P29 (P = 0.0645);Gain of catalytic residue at P29 (P = 0.0645);
MVP		0.42
MPC		0.21
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.062
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr6-46655951;