3-57557113-G-C

Position:

• chr3-57557113-G-C

Variant summary

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

The NM_177966.7(PDE12):​c.734G>C​(p.Arg245Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE12 NM_177966.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

Genes affected

PDE12 (HGNC:25386): (phosphodiesterase 12) Enables 3'-5'-exoribonuclease activity. Involved in several processes, including RNA metabolic process; cellular response to cytokine stimulus; and regulation of mitochondrial mRNA stability. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE12	NM_177966.7	c.734G>C	p.Arg245Thr	missense_variant	1/3	ENST00000311180.9	NP_808881.3
PDE12	NM_001322176.2	c.734G>C	p.Arg245Thr	missense_variant	1/3		NP_001309105.1
PDE12	NM_001322177.2	c.734G>C	p.Arg245Thr	missense_variant	1/2		NP_001309106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE12	ENST00000311180.9	c.734G>C	p.Arg245Thr	missense_variant	1/3	1	NM_177966.7	ENSP00000309142.7
PDE12	ENST00000487257.1	c.734G>C	p.Arg245Thr	missense_variant	1/2	1		ENSP00000420626.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Jul 15, 2024

The c.734G>C (p.R245T) alteration is located in exon 1 (coding exon 1) of the PDE12 gene. This alteration results from a G to C substitution at nucleotide position 734, causing the arginine (R) at amino acid position 245 to be replaced by a threonine (T). 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	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.085	T;T
Eigen	Benign	0.013
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.8	D;N
REVEL	Benign	0.21
Sift	Benign	0.032	D;T
Sift4G	Uncertain	0.043	D;T
Polyphen		0.51	P;B
Vest4		0.73
MutPred		0.44		Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP		0.47
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.62
gMVP		0.77

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: chr3-57542840;