6-165336155-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001385079.1(PDE10A):ā€‹c.3033C>Gā€‹(p.Leu1011=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,932 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.0072 ( 13 hom., cov: 32)
Exomes š‘“: 0.00079 ( 13 hom. )

Consequence

PDE10A
NM_001385079.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.00800
Variant links:
Genes affected
PDE10A (HGNC:8772): (phosphodiesterase 10A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the corresponding nucleoside 5' monophosphate, but has higher affinity for cAMP, and is more efficient with cAMP as substrate. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 6-165336155-G-C is Benign according to our data. Variant chr6-165336155-G-C is described in ClinVar as [Benign]. Clinvar id is 786541.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-165336155-G-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.008 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00722 (1100/152300) while in subpopulation AFR AF= 0.0252 (1048/41556). AF 95% confidence interval is 0.024. There are 13 homozygotes in gnomad4. There are 533 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PDE10ANM_001385079.1 linkuse as main transcriptc.3033C>G p.Leu1011= synonymous_variant 21/22 ENST00000539869.4 NP_001372008.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PDE10AENST00000539869.4 linkuse as main transcriptc.3033C>G p.Leu1011= synonymous_variant 21/221 NM_001385079.1 ENSP00000438284 P3

Frequencies

GnomAD3 genomes
AF:
0.00722
AC:
1099
AN:
152182
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0253
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
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:
0.0000735
Gnomad OTH
AF:
0.00573
GnomAD3 exomes
AF:
0.00174
AC:
437
AN:
251360
Hom.:
6
AF XY:
0.00126
AC XY:
171
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.0245
Gnomad AMR exome
AF:
0.000723
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.000790
AC:
1154
AN:
1461632
Hom.:
13
Cov.:
30
AF XY:
0.000633
AC XY:
460
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.0278
Gnomad4 AMR exome
AF:
0.00110
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.00187
GnomAD4 genome
AF:
0.00722
AC:
1100
AN:
152300
Hom.:
13
Cov.:
32
AF XY:
0.00716
AC XY:
533
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0252
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00567
Alfa
AF:
0.00221
Hom.:
0
Bravo
AF:
0.00818
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PDE10A-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJan 02, 2020This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 15, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
4.3
DANN
Benign
0.65

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: rs143718875; hg19: chr6-165749644; API