Genetic Variant TDRD6:p.Glu49Gly (chr6-46688274-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001010870.3(TDRD6):c.146A>G(p.Glu49Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000266 in 1,502,578 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

TDRD6
NM_001010870.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

Publications

0 publications found

Variant links:

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 links:

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

TDRD6-AS1 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TDRD6	NM_001010870.3	MANE Select	c.146A>G	p.Glu49Gly	missense	Exon 1 of 4	NP_001010870.1	O60522-1
TDRD6	NM_001168359.2		c.146A>G	p.Glu49Gly	missense	Exon 1 of 3	NP_001161831.1	O60522-2
TDRD6	NR_144468.2		n.1372+6635A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TDRD6	ENST00000316081.11	TSL:1 MANE Select	c.146A>G	p.Glu49Gly	missense	Exon 1 of 4	ENSP00000346065.5	O60522-1
TDRD6	ENST00000544460.5	TSL:2	c.146A>G	p.Glu49Gly	missense	Exon 1 of 3	ENSP00000443299.1	O60522-2
TDRD6-AS1	ENST00000434329.3	TSL:3	n.22T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000222

AC:

AN:

1350610

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

665680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28108

American (AMR)

AF:

0.00

AC:

AN:

28960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22968

East Asian (EAS)

AF:

0.00

AC:

AN:

34078

South Asian (SAS)

AF:

0.00

AC:

AN:

74778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4938

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1066142

Other (OTH)

AF:

0.0000178

AC:

AN:

56198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67946

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000221

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.26

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.1

PhyloP100

3.7

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.16

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.43

MutPred

0.48

Loss of stability (P = 0.0179)

MVP

0.56

MPC

0.24

ClinPred

0.99

GERP RS

4.0

PromoterAI

0.045

Neutral

(source)

Varity_R

0.38

gMVP

0.60

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over