Variant 2-26927265-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_020134.4(DPYSL5):c.433A>T(p.Met145Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DPYSL5
NM_020134.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

Variant links:

Genes affected

DPYSL5 (HGNC:20637): (dihydropyrimidinase like 5) This gene encodes a member of the CRMP (collapsing response mediator protein) family thought to be involved in neural development. Antibodies to the encoded protein were found in some patients with neurologic symptoms who had paraneoplastic syndrome. A pseudogene of this gene is found on chromosome 11. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Dec 2011]

DPYSL5 links:

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;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DPYSL5. . Gene score misZ 3.0829 (greater than the threshold 3.09). Trascript score misZ 3.7328 (greater than threshold 3.09). GenCC has associacion of gene with Ritscher-Schinzel syndrome 4, syndromic intellectual disability.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL5	NM_020134.4 linkuse as main transcript	c.433A>T	p.Met145Leu	missense_variant	4/13	ENST00000288699.11	NP_064519.2	Q9BPU6
DPYSL5	NM_001253723.2 linkuse as main transcript	c.433A>T	p.Met145Leu	missense_variant	4/13		NP_001240652.1	Q9BPU6
DPYSL5	NM_001253724.2 linkuse as main transcript	c.433A>T	p.Met145Leu	missense_variant	4/13		NP_001240653.1	Q9BPU6
DPYSL5	XM_024453007.2 linkuse as main transcript	c.433A>T	p.Met145Leu	missense_variant	4/13		XP_024308775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL5	ENST00000288699.11 linkuse as main transcript	c.433A>T	p.Met145Leu	missense_variant	4/13	1	NM_020134.4	ENSP00000288699.6		Q9BPU6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250322

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00000137

AC:

AN:

1461408

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2024

In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.35

.;T;T;T;T;.

Eigen

Benign

-0.054

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;.;.;D;D;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.47

T;T;T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

0.59

.;N;N;.;N;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.5

N;N;N;N;.;N

REVEL

Uncertain

0.40

Sift

Benign

0.37

T;T;T;T;.;T

Sift4G

Benign

0.45

T;T;T;T;T;T

Polyphen

0.017

.;B;B;.;B;.

Vest4

0.48, 0.48

MutPred

0.55

Loss of catalytic residue at V141 (P = 0.0215);Loss of catalytic residue at V141 (P = 0.0215);Loss of catalytic residue at V141 (P = 0.0215);Loss of catalytic residue at V141 (P = 0.0215);Loss of catalytic residue at V141 (P = 0.0215);Loss of catalytic residue at V141 (P = 0.0215);

MVP

0.54

MPC

1.6

ClinPred

0.72

GERP RS

5.5

Varity_R

0.62

gMVP

0.95

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.

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