Variant 5-147412679-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001197294.2(DPYSL3):c.892A>G(p.Ile298Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,994 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DPYSL3
NM_001197294.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

Variant links:

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]

DPYSL3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032442868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DPYSL3	NM_001197294.2 linkuse as main transcript	c.892A>G	p.Ile298Val	missense_variant	6/14	ENST00000343218.10
DPYSL3	NM_001387.3 linkuse as main transcript	c.550A>G	p.Ile184Val	missense_variant	6/14
DPYSL3	XM_011537574.3 linkuse as main transcript	c.538A>G	p.Ile180Val	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL3	ENST00000343218.10 linkuse as main transcript	c.892A>G	p.Ile298Val	missense_variant	6/14	1	NM_001197294.2		Q14195-2
DPYSL3	ENST00000398514.7 linkuse as main transcript	c.550A>G	p.Ile184Val	missense_variant	6/14	1		P1	Q14195-1
DPYSL3	ENST00000519672.1 linkuse as main transcript	n.432A>G		non_coding_transcript_exon_variant	5/6	3
DPYSL3	ENST00000507309.5 linkuse as main transcript	n.96-13427A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000614

AC:

AN:

244182

Hom.:

AF XY:

0.0000453

AC XY:

AN XY:

132338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000839

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:

0.00000411

AC:

AN:

1458994

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

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

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000745

AC:

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

May 22, 2023

The c.892A>G (p.I298V) alteration is located in exon 6 (coding exon 6) of the DPYSL3 gene. This alteration results from a A to G substitution at nucleotide position 892, causing the isoleucine (I) at amino acid position 298 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

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

-0.085

N;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.26

Sift

Benign

1.0

T;T

Sift4G

Benign

0.97

T;T

Polyphen

0.0010

B;.

Vest4

0.20

MutPred

0.48

Gain of catalytic residue at I184 (P = 0.0222);.;

MVP

0.17

MPC

0.45

ClinPred

0.033

GERP RS

4.9

Varity_R

0.061

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over