19-32742881-C-G

Position:

• chr19-32742881-C-G

Variant summary

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

The NM_001366102.1(TDRD12):​c.421C>G​(p.Arg141Gly) 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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TDRD12 NM_001366102.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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=0.12653545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD12	NM_001366102.1	c.421C>G	p.Arg141Gly	missense_variant	4/33	ENST00000639142.2	NP_001353031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD12	ENST00000639142.2	c.421C>G	p.Arg141Gly	missense_variant	4/33	5	NM_001366102.1	ENSP00000492643	A2
TDRD12	ENST00000444215.6	c.421C>G	p.Arg141Gly	missense_variant	4/28	1		ENSP00000416248
TDRD12	ENST00000647536.1	c.421C>G	p.Arg141Gly	missense_variant	4/33			ENSP00000496698	P4
TDRD12	ENST00000421545.2	c.421C>G	p.Arg141Gly	missense_variant	4/13	5		ENSP00000390621

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 07, 2024

The c.421C>G (p.R141G) alteration is located in exon 4 (coding exon 4) of the TDRD12 gene. This alteration results from a C to G substitution at nucleotide position 421, causing the arginine (R) at amino acid position 141 to be replaced by a glycine (G). 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	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.0015	T;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.92	N;.;N
REVEL	Benign	0.024
Sift	Benign	0.26	T;.;T
Sift4G	Uncertain	0.015	D;.;T
Polyphen		0.010	B;.;.
Vest4		0.16
MutPred		0.29		Loss of solvent accessibility (P = 0.01);Loss of solvent accessibility (P = 0.01);Loss of solvent accessibility (P = 0.01);
MVP		0.040
ClinPred		0.78	D
GERP RS		3.2
Varity_R		0.099

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: chr19-33233787;