13-60460500-A-C

Variant summary

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

The NM_001146070.2(TDRD3):c.313A>C(p.Ser105Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,427,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TDRD3 NM_001146070.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13

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]

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/exons	MANE	UniProt
TDRD3	NM_001146070.2	c.313A>C	p.Ser105Arg	missense_variant	4/14	ENST00000377881.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD3	ENST00000377881.8	c.313A>C	p.Ser105Arg	missense_variant	4/14	1	NM_001146070.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1427032 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 709584

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: 0.0000126

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

Jan 24, 2024

The c.313A>C (p.S105R) alteration is located in exon 4 (coding exon 4) of the TDRD3 gene. This alteration results from a A to C substitution at nucleotide position 313, causing the serine (S) at amino acid position 105 to be replaced by an arginine (R). 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
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.049	T;T;.;T;T;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;.;D;.;.;D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Uncertain	2.6	M;M;.;M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N;N;N;N;.;.;D
REVEL	Uncertain	0.52
Sift	Benign	0.050	D;D;D;D;.;.;D
Sift4G	Uncertain	0.036	D;D;D;D;.;D;T
Polyphen		0.72	P;P;D;P;P;P;.
Vest4		0.69
MutPred		0.43		Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);.;Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);
MVP		0.95
MPC		0.19
ClinPred		0.94	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.72

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: chr13-61034634;