Genetic Variant DPYSL4:p.Ala127Val (chr10-132194911-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006426.3(DPYSL4):c.380C>T(p.Ala127Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A127G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DPYSL4
NM_006426.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.59

Publications

2 publications found

Variant links:

Genes affected

DPYSL4 (HGNC:3016): (dihydropyrimidinase like 4) Enables filamin binding activity. Predicted to be involved in nervous system development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

DPYSL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.963

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006426.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL4	NM_006426.3	MANE Select	c.380C>T	p.Ala127Val	missense	Exon 4 of 14	NP_006417.2	O14531

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPYSL4	ENST00000338492.9	TSL:1 MANE Select	c.380C>T	p.Ala127Val	missense	Exon 4 of 14	ENSP00000339850.3	O14531
DPYSL4	ENST00000905073.1		c.380C>T	p.Ala127Val	missense	Exon 4 of 14	ENSP00000575132.1
DPYSL4	ENST00000905072.1		c.380C>T	p.Ala127Val	missense	Exon 4 of 14	ENSP00000575131.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

247882

AF XY:

0.00000743

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1460212

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111882

Other (OTH)

AF:

0.0000331

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.45

MetaRNN

Pathogenic

0.96

MetaSVM

Uncertain

0.74

MutationAssessor

Pathogenic

3.2

PhyloP100

7.6

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.5

REVEL

Pathogenic

0.81

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

0.80

Vest4

0.89

MutPred

0.77

Loss of disorder (P = 0.0714)

MVP

0.95

MPC

0.34

ClinPred

0.97

GERP RS

4.5

Varity_R

0.84

gMVP

0.89

Mutation Taster

=52/48

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over