19-32738860-G-A

Variant names:

• chr19-32738860-G-A
• rs1196825700
• NM_001366102.1:c.188G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001366102.1(TDRD12):​c.188G>A​(p.Cys63Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,398,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C63F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TDRD12 NM_001366102.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366102.1. 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
	TDRD12	NM_001366102.1	MANE Select	c.188G>A	p.Cys63Tyr	missense	Exon 3 of 33	NP_001353031.1	A0A1W2PRK2
	TDRD12	NM_001437947.1		c.188G>A	p.Cys63Tyr	missense	Exon 3 of 33	NP_001424876.1	A0A2R8Y872
	TDRD12	NM_001438799.1		c.188G>A	p.Cys63Tyr	missense	Exon 3 of 33	NP_001425728.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD12	ENST00000639142.2	TSL:5 MANE Select	c.188G>A	p.Cys63Tyr	missense	Exon 3 of 33	ENSP00000492643.2	A0A1W2PRK2
	TDRD12	ENST00000444215.6	TSL:1	c.188G>A	p.Cys63Tyr	missense	Exon 3 of 28	ENSP00000416248.2	Q587J7-1
	TDRD12	ENST00000647536.1		c.188G>A	p.Cys63Tyr	missense	Exon 3 of 33	ENSP00000496698.1	A0A2R8Y872

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398644 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 689866

African (AFR) AF: 0.0000317 AC: 1 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5270

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078890

Other (OTH) AF: 0.00 AC: 0 AN: 57936

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-1.1	T
PhyloP100		4.8
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.76		Gain of sheet (P = 0.1208)
MVP		0.19
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.90
Mutation Taster		=60/40	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

dbSNP: rs1196825700; hg19: chr19-33229766;