rs1056537

Variant names:

• chr3-57563354-C-A
• rs1056537
• NM_177966.7:c.*3350C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-57563354-C-A
• chr3-57563354-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177966.7(PDE12):​c.*3350C>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE12 NM_177966.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 1 publications found

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]

PDE12 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE12	NM_177966.7	c.*3350C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000311180.9	NP_808881.3
PDE12	NM_001322177.2	c.*3934C>A		3_prime_UTR_variant	Exon 2 of 2		NP_001309106.1
PDE12	NM_001322176.2	c.1387+3966C>A		intron_variant	Intron 2 of 2		NP_001309105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE12	ENST00000311180.9	c.*3350C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_177966.7	ENSP00000309142.7
PDE12	ENST00000715954.1	c.1387+3966C>A		intron_variant	Intron 2 of 2			ENSP00000520545.1
PDE12	ENST00000715955.1	c.1387+3966C>A		intron_variant	Intron 2 of 3			ENSP00000520546.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.25
PhyloP100		-1.3

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: rs1056537; hg19: chr3-57549081;