19-32738917-C-A

Variant names:

• chr19-32738917-C-A
• NM_001366102.1:c.245C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366102.1(TDRD12):​c.245C>A​(p.Thr82Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TDRD12 NM_001366102.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.792

Genes affected

TDRD12 (HGNC:25044): (tudor domain containing 12) Predicted to enable ATP binding activity; RNA helicase activity; and nucleic acid binding activity. Predicted to be involved in several processes, including gamete generation; gene silencing by RNA; and piRNA metabolic process. Predicted to be part of PET complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15504125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD12	NM_001366102.1	c.245C>A	p.Thr82Lys	missense_variant	Exon 3 of 33	ENST00000639142.2	NP_001353031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD12	ENST00000639142.2	c.245C>A	p.Thr82Lys	missense_variant	Exon 3 of 33	5	NM_001366102.1	ENSP00000492643.2
TDRD12	ENST00000444215.6	c.245C>A	p.Thr82Lys	missense_variant	Exon 3 of 28	1		ENSP00000416248.2
TDRD12	ENST00000647536.1	c.245C>A	p.Thr82Lys	missense_variant	Exon 3 of 33			ENSP00000496698.1
TDRD12	ENST00000421545.2	c.245C>A	p.Thr82Lys	missense_variant	Exon 3 of 13	5		ENSP00000390621.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399072 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690040

Gnomad4 AFR exome AF: 0.00

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: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.245C>A (p.T82K) alteration is located in exon 3 (coding exon 3) of the TDRD12 gene. This alteration results from a C to A substitution at nucleotide position 245, causing the threonine (T) at amino acid position 82 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.0011	T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.26	T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.96	N;.;N
REVEL	Benign	0.071
Sift	Benign	0.035	D;.;D
Sift4G	Uncertain	0.016	D;.;D
Polyphen		0.0020	B;.;.
Vest4		0.25
MutPred		0.49		Gain of ubiquitination at T82 (P = 0.023);Gain of ubiquitination at T82 (P = 0.023);Gain of ubiquitination at T82 (P = 0.023);
MVP		0.030
ClinPred		0.71	D
GERP RS		4.6
Varity_R		0.054

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: chr19-33229823;