8-65719297-A-G

Position:

• chr8-65719297-A-G

Variant summary

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

The NM_001242318.3(PDE7A):​c.1442T>C​(p.Leu481Ser) 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. 15/21 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)
• Consequence: PDE7A NM_001242318.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

Genes affected

PDE7A (HGNC:8791): (phosphodiesterase 7A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE7 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2011]

MTFR1 (HGNC:29510): (mitochondrial fission regulator 1) This gene encodes a mitochondrial protein that is characterized by a poly-proline rich region. A chicken homolog of this protein promotes mitochondrial fission and the mouse homolog protects cells from oxidative stress. A related pseudogene of this gene is found on chromosome X. [provided by RefSeq, Mar 2009]

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=0.11432478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE7A	NM_001242318.3	c.1442T>C	p.Leu481Ser	missense_variant	13/13	ENST00000401827.8	NP_001229247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE7A	ENST00000401827.8	c.1442T>C	p.Leu481Ser	missense_variant	13/13	1	NM_001242318.3	ENSP00000385632	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Mar 01, 2024

The c.1442T>C (p.L481S) alteration is located in exon 1 (coding exon 1) of the PDE7A gene. This alteration results from a T to C substitution at nucleotide position 1442, causing the leucine (L) at amino acid position 481 to be replaced by a serine (S). 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	0.067
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	0.87	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.10
Sift	Benign	0.088	T;T
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.0	B;B
Vest4		0.15
MutPred		0.23		Loss of stability (P = 0.0037);.;
MVP		0.66
MPC		0.71
ClinPred		0.25	T
GERP RS		2.0
Varity_R		0.034
gMVP		0.34

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: chr8-66631532;