NM_001395205.1:c.257C>T

Variant names:

• chr10-114188088-C-T
• NM_001395205.1:c.257C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395205.1(TDRD1):​c.257C>T​(p.Ser86Phe) 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. 13/21 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: TDRD1 NM_001395205.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

Genes affected

TDRD1 (HGNC:11712): (tudor domain containing 1) This gene encodes a protein containing a tudor domain that is thought to function in the suppression of transposable elements during spermatogenesis. The related protein in mouse forms a complex with piRNAs and Piwi proteins to promote methylation and silencing of target sequences. This gene was observed to be upregulated by ETS transcription factor ERG in prostate tumors. [provided by RefSeq, Sep 2018]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29586342).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395205.1. 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
	TDRD1	NM_001395205.1	MANE Select	c.257C>T	p.Ser86Phe	missense	Exon 2 of 25	NP_001382134.1	Q9BXT4-1
	TDRD1	NM_001385363.1		c.257C>T	p.Ser86Phe	missense	Exon 2 of 26	NP_001372292.1	Q9BXT4-3
	TDRD1	NM_198795.2		c.257C>T	p.Ser86Phe	missense	Exon 2 of 26	NP_942090.1	Q9BXT4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD1	ENST00000695399.1	MANE Select	c.257C>T	p.Ser86Phe	missense	Exon 2 of 25	ENSP00000511878.1	Q9BXT4-1
	TDRD1	ENST00000251864.7	TSL:1	c.257C>T	p.Ser86Phe	missense	Exon 2 of 26	ENSP00000251864.2	Q9BXT4-3
	TDRD1	ENST00000952550.1		c.257C>T	p.Ser86Phe	missense	Exon 2 of 25	ENSP00000622609.1

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	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.090
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.17		Gain of sheet (P = 0.0477)
MVP		0.30
MPC		0.74
ClinPred		0.94	D
GERP RS		5.8
gMVP		0.34
Mutation Taster		=287/13	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: chr10-115947847;