rs199604826

Variant names:

• chr1-179592781-C-A
• rs199604826
• NM_001199085.3:c.166C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-179592781-C-A
• chr1-179592781-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001199085.3(TDRD5):​c.166C>A​(p.Leu56Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L56V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TDRD5 NM_001199085.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2713154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD5	NM_001199085.3	c.166C>A	p.Leu56Met	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.166C>A	p.Leu56Met	missense_variant	Exon 2 of 18	1	NM_001199085.3	ENSP00000406052.1
TDRD5	ENST00000294848.12	c.166C>A	p.Leu56Met	missense_variant	Exon 2 of 17	1		ENSP00000294848.8
TDRD5	ENST00000367614.5	c.166C>A	p.Leu56Met	missense_variant	Exon 2 of 17	2		ENSP00000356586.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;.;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.15	T;T;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.40
MutPred		0.51		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.043
MPC		0.64
ClinPred		0.93	D
GERP RS		0.92
Varity_R		0.18
gMVP		0.61

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: rs199604826; hg19: chr1-179561916;