6-105159825-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The ENST00000254765.4(POPDC3):​c.486-6T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,590,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

POPDC3
ENST00000254765.4 splice_region, splice_polypyrimidine_tract, intron

Scores

1
4
9
Splicing: ADA: 0.9999
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.90
Variant links:
Genes affected
POPDC3 (HGNC:17649): (popeye domain containing 3) This gene encodes a member of the POP family of proteins containing three putative transmembrane domains. This gene is expressed in cardiac and skeletal muscle and may play an important role in these tissues during development. Alternatively spliced transcript variants have been found. [provided by RefSeq, Nov 2008]
BVES-AS1 (HGNC:21223): (BVES antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-105159825-A-T is Pathogenic according to our data. Variant chr6-105159825-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 3069145.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POPDC3NM_022361.5 linkuse as main transcriptc.486-6T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000254765.4 NP_071756.2
BVES-AS1NR_037157.1 linkuse as main transcriptn.343-6719A>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POPDC3ENST00000254765.4 linkuse as main transcriptc.486-6T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_022361.5 ENSP00000254765 P1
BVES-AS1ENST00000687937.1 linkuse as main transcriptn.342+12445A>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250896
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000243
AC:
35
AN:
1438322
Hom.:
0
Cov.:
25
AF XY:
0.0000279
AC XY:
20
AN XY:
717244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000293
Gnomad4 OTH exome
AF:
0.0000503
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Muscular dystrophy, limb-girdle, autosomal recessive 26 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 11, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
23
DANN
Uncertain
0.98
Eigen
Pathogenic
0.72
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.39
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D
PROVEAN
Benign
0.45
N
REVEL
Benign
0.042
Sift
Benign
0.12
T
Sift4G
Uncertain
0.043
D
MutPred
0.46
Loss of sheet (P = 0.0084);
MVP
0.16
ClinPred
0.081
T
GERP RS
3.4

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.95
SpliceAI score (max)
0.92
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.92
Position offset: -2
DS_AL_spliceai
0.45
Position offset: -6

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: rs1478322852; hg19: chr6-105607700; API