dbSNP rs149546549: PHAX:p.Asp19Asn (chr5-126601017-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032177.4(PHAX):c.55G>A(p.Asp19Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,454,554 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: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PHAX
NM_032177.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.21

Variant links:

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 links:

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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 rank	MANE	Protein	UniProt
PHAX	NM_032177.4 link	c.55G>A	p.Asp19Asn	missense_variant	Exon 1 of 5	ENST00000297540.5	NP_115553.2	Q9H814

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHAX	ENST00000297540.5 link	c.55G>A	p.Asp19Asn	missense_variant	Exon 1 of 5	1	NM_032177.4	ENSP00000297540.4		Q9H814
PHAX	ENST00000514725.1 link	n.93G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000207

AC:

AN:

241960

Hom.:

AF XY:

0.00000759

AC XY:

AN XY:

131760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1454554

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

723828

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:

0.0000188

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.61

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.6

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.2

REVEL

Benign

0.20

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

0.99

Vest4

0.26

MutPred

0.30

Gain of sheet (P = 0.0036);

MVP

0.70

MPC

0.44

ClinPred

0.81

GERP RS

4.6

Varity_R

0.34

gMVP

0.20

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over