NM_001010870.3:c.92A>C

Variant names:

• chr6-46688220-A-C
• NM_001010870.3:c.92A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010870.3(TDRD6):​c.92A>C​(p.Gln31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TDRD6 NM_001010870.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01
• Publications: 0 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-AS1 (HGNC:56119): (TDRD6 and SLC25A27 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010870.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD6	NM_001010870.3	MANE Select	c.92A>C	p.Gln31Pro	missense	Exon 1 of 4	NP_001010870.1	O60522-1
	TDRD6	NM_001168359.2		c.92A>C	p.Gln31Pro	missense	Exon 1 of 3	NP_001161831.1	O60522-2
	TDRD6	NR_144468.2		n.1372+6581A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD6	ENST00000316081.11	TSL:1 MANE Select	c.92A>C	p.Gln31Pro	missense	Exon 1 of 4	ENSP00000346065.5	O60522-1
	TDRD6	ENST00000544460.5	TSL:2	c.92A>C	p.Gln31Pro	missense	Exon 1 of 3	ENSP00000443299.1	O60522-2
	TDRD6-AS1	ENST00000434329.3	TSL:3	n.76T>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.0022	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.27
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.74		Loss of catalytic residue at Q31 (P = 0.0473)
MVP		0.47
MPC		0.21
ClinPred		0.87	D
GERP RS		4.0
PromoterAI		-0.0018	Neutral
Varity_R		0.50
gMVP		0.86
Mutation Taster		=71/29	polymorphism

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

hg19: chr6-46655957;