Variant chr19-53636842-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012728.2(DPRX):c.430T>A(p.Phe144Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000082 ( 0 hom. )

Consequence

DPRX
NM_001012728.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.154

Variant links:

Genes affected

DPRX (HGNC:32166): (divergent-paired related homeobox) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the DPRX homeobox gene family. Evidence of mRNA expression has not yet been found for this gene. Multiple, related processed pseudogenes have been found which are thought to reflect expression of this gene in the germ line or embryonic cells. [provided by RefSeq, Jul 2008]

DPRX links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12327874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPRX	NM_001012728.2 link	c.430T>A	p.Phe144Ile	missense_variant	Exon 3 of 3	ENST00000376650.2	NP_001012746.1	A6NFQ7
DPRX	XM_011527011.4 link	c.430T>A	p.Phe144Ile	missense_variant	Exon 4 of 4		XP_011525313.1	A6NFQ7
DPRX	XM_011527012.3 link	c.430T>A	p.Phe144Ile	missense_variant	Exon 4 of 4		XP_011525314.1	A6NFQ7
DPRX	XM_047438893.1 link	c.430T>A	p.Phe144Ile	missense_variant	Exon 4 of 4		XP_047294849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPRX	ENST00000376650.2 link	c.430T>A	p.Phe144Ile	missense_variant	Exon 3 of 3	3	NM_001012728.2	ENSP00000365838.1		A6NFQ7
DPRX	ENST00000710707.1 link	c.430T>A	p.Phe144Ile	missense_variant	Exon 5 of 5			ENSP00000518423.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251486

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

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:

0.00000821

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

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

ExAC

AF:

0.0000165

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

Mar 19, 2024

The c.430T>A (p.F144I) alteration is located in exon 3 (coding exon 3) of the DPRX gene. This alteration results from a T to A substitution at nucleotide position 430, causing the phenylalanine (F) at amino acid position 144 to be replaced by an isoleucine (I). 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

0.082

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.18

CADD

Benign

5.5

DANN

Benign

0.92

DEOGEN2

Benign

0.012

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.31

M_CAP

Benign

0.0074

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.71

REVEL

Benign

0.28

Sift

Benign

0.075

Sift4G

Benign

0.11

Polyphen

0.74

Vest4

0.28

MutPred

0.49

Loss of catalytic residue at F144 (P = 0.067);

MVP

0.42

MPC

0.31

ClinPred

0.068

GERP RS

1.4

Varity_R

0.053

gMVP

0.17

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