chr10-114187973-C-G

Position:

• chr10-114187973-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395205.1(TDRD1):​c.142C>G​(p.Pro48Ala) 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. 14/19 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: 0.549

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038647205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD1	NM_001395205.1	c.142C>G	p.Pro48Ala	missense_variant	2/25	ENST00000695399.1	NP_001382134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD1	ENST00000695399.1	c.142C>G	p.Pro48Ala	missense_variant	2/25		NM_001395205.1	ENSP00000511878.1
TDRD1	ENST00000251864.7	c.142C>G	p.Pro48Ala	missense_variant	2/26	1		ENSP00000251864.2
TDRD1	ENST00000369282.5	c.142C>G	p.Pro48Ala	missense_variant	2/25	5		ENSP00000358288.1
TDRD1	ENST00000369280.1	c.142C>G	p.Pro48Ala	missense_variant	2/24	5		ENSP00000358286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251332 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135838

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

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

Jun 17, 2024

The c.142C>G (p.P48A) alteration is located in exon 2 (coding exon 1) of the TDRD1 gene. This alteration results from a C to G substitution at nucleotide position 142, causing the proline (P) at amino acid position 48 to be replaced by an alanine (A). 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	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.23
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.039	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.51	.;N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.74	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.99	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0050	.;B;.
Vest4		0.15
MutPred		0.12		Loss of relative solvent accessibility (P = 0.0306);Loss of relative solvent accessibility (P = 0.0306);Loss of relative solvent accessibility (P = 0.0306);
MVP		0.27
MPC		0.68
ClinPred		0.054	T
GERP RS		1.6
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs1199985160; hg19: chr10-115947732;