19-32756053-A-C

Variant names:

• chr19-32756053-A-C
• rs1019504812
• NM_001366102.1:c.644A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366102.1(TDRD12):​c.644A>C​(p.Asn215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000196 in 1,329,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.000020 (0 hom.)
• Consequence: TDRD12 NM_001366102.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.462
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09710902).

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.644A>C	p.Asn215Thr	missense	Exon 7 of 33	NP_001353031.1	A0A1W2PRK2
	TDRD12	NM_001437947.1		c.644A>C	p.Asn215Thr	missense	Exon 7 of 33	NP_001424876.1	A0A2R8Y872
	TDRD12	NM_001438799.1		c.644A>C	p.Asn215Thr	missense	Exon 7 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.644A>C	p.Asn215Thr	missense	Exon 7 of 33	ENSP00000492643.2	A0A1W2PRK2
	TDRD12	ENST00000444215.6	TSL:1	c.644A>C	p.Asn215Thr	missense	Exon 7 of 28	ENSP00000416248.2	Q587J7-1
	TDRD12	ENST00000647536.1		c.644A>C	p.Asn215Thr	missense	Exon 7 of 33	ENSP00000496698.1	A0A2R8Y872

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000106 AC: 1 AN: 93908 AF XY: 0.0000197

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000240

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000196 AC: 26 AN: 1329762 Hom.: 0 Cov.: 30 AF XY: 0.0000168 AC XY: 11 AN XY: 654386

African (AFR) AF: 0.00 AC: 0 AN: 26678

American (AMR) AF: 0.00 AC: 0 AN: 17272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23208

East Asian (EAS) AF: 0.00 AC: 0 AN: 31182

South Asian (SAS) AF: 0.00 AC: 0 AN: 66414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 0.0000246 AC: 26 AN: 1055518

Other (OTH) AF: 0.00 AC: 0 AN: 55154

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.088
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.6
DANN	Benign	0.97
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.46
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.052
Sift	Benign	0.17	T
Sift4G	Benign	0.068	T
Polyphen		0.29	B
Vest4		0.15
MutPred		0.32		Gain of phosphorylation at N215 (P = 0.0374)
MVP		0.014
ClinPred		0.089	T
GERP RS		0.93
Varity_R		0.067
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1019504812; hg19: chr19-33246959;