Variant 5-126603658-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000297540.5(PHAX):c.185G>A(p.Ser62Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

PHAX
ENST00000297540.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027720094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHAX	NM_032177.4 linkuse as main transcript	c.185G>A	p.Ser62Asn	missense_variant	2/5	ENST00000297540.5	NP_115553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PHAX	ENST00000297540.5 linkuse as main transcript	c.185G>A	p.Ser62Asn	missense_variant	2/5	1	NM_032177.4	ENSP00000297540	P1
PHAX	ENST00000505674.5 linkuse as main transcript	n.98G>A		non_coding_transcript_exon_variant	1/3	2
PHAX	ENST00000514725.1 linkuse as main transcript	n.219G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251492

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000189

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

Sep 14, 2021

The c.185G>A (p.S62N) 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 185, causing the serine (S) at amino acid position 62 to be replaced by an asparagine (N). 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

0.074

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.013

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.56

M_CAP

Benign

0.0066

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.0

REVEL

Benign

0.027

Sift

Benign

0.36

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.085

MVP

0.17

MPC

0.085

ClinPred

0.040

GERP RS

3.0

Varity_R

0.031

gMVP

0.077

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over