8-65734889-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242318.3(PDE7A):ā€‹c.601A>Gā€‹(p.Ile201Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000814 in 1,597,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000042 ( 0 hom. )

Consequence

PDE7A
NM_001242318.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12029743).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PDE7ANM_001242318.3 linkuse as main transcriptc.601A>G p.Ile201Val missense_variant 7/13 ENST00000401827.8 NP_001229247.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PDE7AENST00000401827.8 linkuse as main transcriptc.601A>G p.Ile201Val missense_variant 7/131 NM_001242318.3 ENSP00000385632 P4Q13946-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250972
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135642
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000415
AC:
6
AN:
1444904
Hom.:
0
Cov.:
26
AF XY:
0.00000139
AC XY:
1
AN XY:
719742
show subpopulations
Gnomad4 AFR exome
AF:
0.000181
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 02, 2022The c.601A>G (p.I201V) alteration is located in exon 1 (coding exon 1) of the PDE7A gene. This alteration results from a A to G substitution at nucleotide position 601, causing the isoleucine (I) at amino acid position 201 to be replaced by a valine (V). 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
0.083
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
16
DANN
Benign
0.85
DEOGEN2
Benign
0.13
T;.;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.18
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.71
T;T;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.2
N;.;N
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.13
N;N;N
REVEL
Benign
0.13
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.26
MutPred
0.51
Gain of phosphorylation at Y205 (P = 0.0921);.;Gain of phosphorylation at Y205 (P = 0.0921);
MVP
0.63
MPC
0.35
ClinPred
0.17
T
GERP RS
4.8
Varity_R
0.061
gMVP
0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs749772109; hg19: chr8-66647124; API