Genetic Variant NM_005510.4:c.434G>T (chr6-31971070-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005510.4(DXO):c.434G>T(p.Arg145Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. R145Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DXO
NM_005510.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

Publications

0 publications found

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:

WHR1 (HGNC:11398): (serine/threonine kinase 19) This gene encodes a serine/threonine kinase which localizes predominantly to the nucleus. Its specific function is unknown; it is possible that phosphorylation of this protein is involved in transcriptional regulation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants. [provided by RefSeq, Jul 2008]

WHR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.063819796).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DXO	NM_005510.4	MANE Select	c.434G>T	p.Arg145Leu	missense	Exon 3 of 7	NP_005501.2
DXO	NM_001371205.1		c.-119G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_001358134.1
DXO	NM_001371206.1		c.-119G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_001358135.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DXO	ENST00000337523.10	TSL:1 MANE Select	c.434G>T	p.Arg145Leu	missense	Exon 3 of 7	ENSP00000337759.5	O77932
DXO	ENST00000375356.7	TSL:1	c.434G>T	p.Arg145Leu	missense	Exon 2 of 6	ENSP00000364505.3	O77932
DXO	ENST00000473976.1	TSL:1	n.854G>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.050

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.10

M_CAP

Benign

0.0033

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.79

PhyloP100

-0.23

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.2

REVEL

Benign

0.021

Sift

Benign

0.31

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.30

MutPred

0.38

Loss of disorder (P = 0.0881)

MVP

0.20

MPC

0.46

ClinPred

0.24

GERP RS

0.79

PromoterAI

-0.059

Neutral

(source)

Varity_R

0.058

gMVP

0.54

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over