NM_001199085.3:c.499T>A

Variant names:

• chr1-179593726-T-A
• NM_001199085.3:c.499T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001199085.3(TDRD5):​c.499T>A​(p.Tyr167Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TDRD5 NM_001199085.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199085.3. 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
	TDRD5	NM_001199085.3	MANE Select	c.499T>A	p.Tyr167Asn	missense	Exon 3 of 18	NP_001186014.1	Q8NAT2-1
	TDRD5	NM_001199089.3		c.499T>A	p.Tyr167Asn	missense	Exon 3 of 18	NP_001186018.1	Q8NAT2-1
	TDRD5	NM_001199091.2		c.499T>A	p.Tyr167Asn	missense	Exon 3 of 17	NP_001186020.1	Q8NAT2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD5	ENST00000444136.6	TSL:1 MANE Select	c.499T>A	p.Tyr167Asn	missense	Exon 3 of 18	ENSP00000406052.1	Q8NAT2-1
	TDRD5	ENST00000294848.12	TSL:1	c.499T>A	p.Tyr167Asn	missense	Exon 3 of 17	ENSP00000294848.8	Q8NAT2-3
	TDRD5	ENST00000367614.5	TSL:2	c.499T>A	p.Tyr167Asn	missense	Exon 3 of 17	ENSP00000356586.1	Q8NAT2-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

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	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.52		Gain of MoRF binding (P = 0.0737)
MVP		0.23
MPC		1.0
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.56
gMVP		0.84
Mutation Taster		=76/24	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: chr1-179562861;