chr5-126604041-G-A

Position:

• chr5-126604041-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032177.4(PHAX):​c.568G>A​(p.Glu190Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHAX NM_032177.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.58

Genes affected

PHAX (HGNC:10241): (phosphorylated adaptor for RNA export) Enables mRNA cap binding complex binding activity. Involved in RNA stabilization. Located in centrosome and nucleoplasm. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

PHAX (HGNC:):

ACMG classification

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=0.17846814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHAX	NM_032177.4	c.568G>A	p.Glu190Lys	missense_variant	2/5	ENST00000297540.5	NP_115553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHAX	ENST00000297540.5	c.568G>A	p.Glu190Lys	missense_variant	2/5	1	NM_032177.4	ENSP00000297540.4
PHAX	ENST00000505674.5	n.481G>A		non_coding_transcript_exon_variant	1/3	2
PHAX	ENST00000514725.1	n.602G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2024

The c.568G>A (p.E190K) alteration is located in exon 2 (coding exon 2) of the PHAX gene. This alteration results from a G to A substitution at nucleotide position 568, causing the glutamic acid (E) at amino acid position 190 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Benign	0.19	T
Sift4G	Benign	0.19	T
Polyphen		0.60	P
Vest4		0.44
MutPred		0.31		Gain of MoRF binding (P = 0.0039);
MVP		0.30
MPC		0.21
ClinPred		0.85	D
GERP RS		5.7
Varity_R		0.12
gMVP		0.37

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: chr5-125939733;