13-60485877-C-G

Variant names:

• chr13-60485877-C-G
• NM_001146070.2:c.646C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146070.2(TDRD3):​c.646C>G​(p.Pro216Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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: 0.139
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06697309).

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.646C>G	p.Pro216Ala	missense	Exon 7 of 14	NP_001139542.1	Q9H7E2-3
	TDRD3	NM_001146071.1		c.367C>G	p.Pro123Ala	missense	Exon 7 of 14	NP_001139543.1	Q9H7E2-1
	TDRD3	NM_030794.2		c.367C>G	p.Pro123Ala	missense	Exon 7 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.646C>G	p.Pro216Ala	missense	Exon 7 of 14	ENSP00000367113.2	Q9H7E2-3
	TDRD3	ENST00000196169.7	TSL:1	c.367C>G	p.Pro123Ala	missense	Exon 7 of 14	ENSP00000196169.3	Q9H7E2-1
	TDRD3	ENST00000621840.4	TSL:1	c.364C>G	p.Pro122Ala	missense	Exon 7 of 14	ENSP00000477993.1	Q9H7E2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Benign	0.057
BayesDel_addAF	Benign	-0.0076	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	7.1
DANN	Benign	0.75
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.067	T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Benign	1.7	L
PhyloP100		0.14
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.20
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.0040	B
Vest4		0.12
MutPred		0.24		Loss of stability (P = 0.033)
MVP		0.80
MPC		0.15
ClinPred		0.065	T
GERP RS		2.8
Varity_R		0.029
gMVP		0.12
Mutation Taster		=70/30	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: chr13-61060011;