13-60460437-G-A

Position:

• chr13-60460437-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000377881.8(TDRD3):​c.250G>A​(p.Asp84Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TDRD3 ENST00000377881.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

Genes affected

TDRD3 (HGNC:20612): (tudor domain containing 3) Enables chromatin binding activity; methylated histone binding activity; and transcription coactivator activity. Predicted to be involved in chromatin organization and positive regulation of transcription, DNA-templated. Located in Golgi apparatus; cytosol; and nucleoplasm. Colocalizes with exon-exon junction complex. [provided by Alliance of Genome Resources, Apr 2022]

TDRD3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD3	NM_001146070.2	c.250G>A	p.Asp84Asn	missense_variant	4/14	ENST00000377881.8	NP_001139542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD3	ENST00000377881.8	c.250G>A	p.Asp84Asn	missense_variant	4/14	1	NM_001146070.2	ENSP00000367113.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1452296 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722370

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.250G>A (p.D84N) alteration is located in exon 4 (coding exon 4) of the TDRD3 gene. This alteration results from a G to A substitution at nucleotide position 250, causing the aspartic acid (D) at amino acid position 84 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	29
DANN	Pathogenic	1.0
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.24
Sift	Benign	0.55	T
Sift4G	Benign	0.39	T
Polyphen		1.0	D
Vest4		0.69
MutPred		0.32		Gain of glycosylation at P82 (P = 0.0774);
MVP		0.67
MPC		0.65
ClinPred		0.95	D
GERP RS		6.1
gMVP		0.49

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: chr13-61034571;