chr5-126600987-G-T

Variant names:

• chr5-126600987-G-T
• rs772299235
• NM_032177.4:c.25G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032177.4(PHAX):​c.25G>T​(p.Glu9*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000689 in 1,452,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PHAX NM_032177.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.78
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032177.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHAX	NM_032177.4	MANE Select	c.25G>T	p.Glu9*	stop_gained	Exon 1 of 5	NP_115553.2	Q9H814

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHAX	ENST00000297540.5	TSL:1 MANE Select	c.25G>T	p.Glu9*	stop_gained	Exon 1 of 5	ENSP00000297540.4	Q9H814
	PHAX	ENST00000852111.1		c.25G>T	p.Glu9*	stop_gained	Exon 1 of 4	ENSP00000522170.1
	PHAX	ENST00000514725.1	TSL:3	n.63G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452252 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722722

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31530

American (AMR) AF: 0.00 AC: 0 AN: 44250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25712

East Asian (EAS) AF: 0.00 AC: 0 AN: 38240

South Asian (SAS) AF: 0.00 AC: 0 AN: 85850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107658

Other (OTH) AF: 0.00 AC: 0 AN: 59962

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	45
DANN	Uncertain	0.99
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.90	D
PhyloP100		6.8
Vest4		0.18
GERP RS		3.0
PromoterAI		-0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Mutation Taster		=6/194	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs772299235; hg19: chr5-125936679;