NM_005510.4:c.554T>A

Variant names:

• chr6-31970950-A-T
• NM_005510.4:c.554T>A

Variant summary

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

The NM_005510.4(DXO):​c.554T>A​(p.Met185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,722 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DXO NM_005510.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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]

STK19 (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]

ACMG classification

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 rank	MANE	Protein	UniProt
DXO	NM_005510.4	c.554T>A	p.Met185Lys	missense_variant	Exon 3 of 7	ENST00000337523.10	NP_005501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DXO	ENST00000337523.10	c.554T>A	p.Met185Lys	missense_variant	Exon 3 of 7	1	NM_005510.4	ENSP00000337759.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460722 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726678

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T;T;T
Eigen	Benign	0.089
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.0055	T
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.079	T;T;T
Sift4G	Benign	0.097	T;T;T
Polyphen		0.52	P;P;P
Vest4		0.60
MutPred		0.66		Loss of stability (P = 0.0419);Loss of stability (P = 0.0419);Loss of stability (P = 0.0419);
MVP		0.43
MPC		0.58
ClinPred		0.86	D
GERP RS		5.2
Varity_R		0.65
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31938727;