chr5-147405696-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001197294.2(DPYSL3):āc.1067T>Cā(p.Ile356Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
DPYSL3
NM_001197294.2 missense
NM_001197294.2 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
DPYSL3 (HGNC:3015): (dihydropyrimidinase like 3) Enables filamin binding activity. Predicted to be involved in several processes, including actin filament organization; regulation of plasma membrane bounded cell projection organization; and response to axon injury. Predicted to act upstream of or within nervous system development. Predicted to be located in several cellular components, including cell body; growth cone; and lamellipodium. Predicted to be part of filamentous actin. Predicted to be active in synapse. Predicted to colocalize with exocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]
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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.802
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPYSL3 | NM_001197294.2 | c.1067T>C | p.Ile356Thr | missense_variant | 8/14 | ENST00000343218.10 | |
DPYSL3 | NM_001387.3 | c.725T>C | p.Ile242Thr | missense_variant | 8/14 | ||
DPYSL3 | XM_011537574.3 | c.713T>C | p.Ile238Thr | missense_variant | 8/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPYSL3 | ENST00000343218.10 | c.1067T>C | p.Ile356Thr | missense_variant | 8/14 | 1 | NM_001197294.2 | ||
DPYSL3 | ENST00000398514.7 | c.725T>C | p.Ile242Thr | missense_variant | 8/14 | 1 | P1 | ||
DPYSL3 | ENST00000508042.1 | n.503T>C | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
DPYSL3 | ENST00000507309.5 | n.96-6444T>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461744Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727172
GnomAD4 exome
AF:
AC:
1
AN:
1461744
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
727172
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
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 submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.1067T>C (p.I356T) alteration is located in exon 8 (coding exon 8) of the DPYSL3 gene. This alteration results from a T to C substitution at nucleotide position 1067, causing the isoleucine (I) at amino acid position 356 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of glycosylation at I242 (P = 0.0302);.;
MVP
MPC
0.76
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at