chr13-60467269-C-T

Variant names:

• chr13-60467269-C-T
• NM_001146070.2:c.385C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001146070.2(TDRD3):​c.385C>T​(p.Leu129Phe) variant causes a missense change. 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)
• Consequence: TDRD3 NM_001146070.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146070.2. 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
	TDRD3	NM_001146070.2	MANE Select	c.385C>T	p.Leu129Phe	missense	Exon 5 of 14	NP_001139542.1	Q9H7E2-3
	TDRD3	NM_001146071.1		c.106C>T	p.Leu36Phe	missense	Exon 5 of 14	NP_001139543.1	Q9H7E2-1
	TDRD3	NM_030794.2		c.106C>T	p.Leu36Phe	missense	Exon 5 of 14	NP_110421.1	Q9H7E2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD3	ENST00000377881.8	TSL:1 MANE Select	c.385C>T	p.Leu129Phe	missense	Exon 5 of 14	ENSP00000367113.2	Q9H7E2-3
	TDRD3	ENST00000196169.7	TSL:1	c.106C>T	p.Leu36Phe	missense	Exon 5 of 14	ENSP00000196169.3	Q9H7E2-1
	TDRD3	ENST00000621840.4	TSL:1	c.106C>T	p.Leu36Phe	missense	Exon 5 of 14	ENSP00000477993.1	Q9H7E2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.60
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N
REVEL	Pathogenic	0.73
Sift	Benign	0.22	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.49		Gain of methylation at K35 (P = 0.0308)
MVP		0.98
MPC		0.68
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.39
gMVP		0.74
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr13-61041403;