Variant 6-31970023-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005510.4(DXO):c.1045C>T(p.Leu349Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DXO
NM_005510.4 missense, splice_region

Scores

Splicing: ADA: 0.03528

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

DXO (HGNC:2992): (decapping exoribonuclease) This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. The function of its protein product is unknown, but its ubiquitous expression and conservation in both simple and complex eukaryotes suggests that this may be a housekeeping gene. [provided by RefSeq, Jul 2008]

DXO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DXO	NM_005510.4 linkuse as main transcript	c.1045C>T	p.Leu349Phe	missense_variant, splice_region_variant	7/7	ENST00000337523.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DXO	ENST00000337523.10 linkuse as main transcript	c.1045C>T	p.Leu349Phe	missense_variant, splice_region_variant	7/7	1	NM_005510.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 08, 2021

The c.1045C>T (p.L349F) alteration is located in exon 7 (coding exon 6) of the DXO gene. This alteration results from a C to T substitution at nucleotide position 1045, causing the leucine (L) at amino acid position 349 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0093

T;T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.78

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.2

M;M;M

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.072

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.50

MutPred

0.49

Gain of catalytic residue at L349 (P = 0.1815);Gain of catalytic residue at L349 (P = 0.1815);Gain of catalytic residue at L349 (P = 0.1815);

MVP

0.61

MPC

1.2

ClinPred

0.87

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.035

dbscSNV1_RF

Benign

0.066

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over