1-179592620-C-G

Variant names:

• chr1-179592620-C-G
• NM_001199085.3:c.5C>G

Variant summary

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

The NM_001199085.3(TDRD5):​c.5C>G​(p.Ser2Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TDRD5 NM_001199085.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

Genes affected

TDRD5 (HGNC:20614): (tudor domain containing 5) Predicted to be involved in DNA methylation involved in gamete generation; P granule organization; and spermatid development. Predicted to be located in chromatoid body and pi-body. [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 rank	MANE	Protein	UniProt
TDRD5	NM_001199085.3	c.5C>G	p.Ser2Cys	missense_variant	Exon 2 of 18	ENST00000444136.6	NP_001186014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD5	ENST00000444136.6	c.5C>G	p.Ser2Cys	missense_variant	Exon 2 of 18	1	NM_001199085.3	ENSP00000406052.1
TDRD5	ENST00000294848.12	c.5C>G	p.Ser2Cys	missense_variant	Exon 2 of 17	1		ENSP00000294848.8
TDRD5	ENST00000367614.5	c.5C>G	p.Ser2Cys	missense_variant	Exon 2 of 17	2		ENSP00000356586.1

Frequencies

GnomAD3 genomes Cov.: 32

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

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5C>G (p.S2C) alteration is located in exon 2 (coding exon 1) of the TDRD5 gene. This alteration results from a C to G substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by a cysteine (C). 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	Benign	0.30
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.55
MutPred		0.29		Loss of phosphorylation at S2 (P = 0.0187);Loss of phosphorylation at S2 (P = 0.0187);Loss of phosphorylation at S2 (P = 0.0187);
MVP		0.23
MPC		0.77
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.29
gMVP		0.51

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: chr1-179561755;