chr9-2777384-T-A

Position:

• chr9-2777384-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000490444.2(PUM3):​c.*126+5372A>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,818 control chromosomes in the GnomAD database, including 13,052 homozygotes. 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: 𝑓 0.40 (13052 hom., cov: 33)
• Consequence: PUM3 ENST00000490444.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

Genes affected

PUM3 (HGNC:29676): (pumilio RNA binding family member 3) Enables RNA binding activity. Involved in regulation of protein ADP-ribosylation. Located in chromosome; endoplasmic reticulum; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUM3	ENST00000490444.2	c.*126+5372A>T		intron_variant, NMD_transcript_variant		5		ENSP00000474467

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60096 AN: 151698 Hom.: 13050 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.396 AC: 60100 AN: 151818 Hom.: 13052 Cov.: 33 AF XY: 0.398 AC XY: 29503 AN XY: 74192

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.407

Alfa AF: 0.320 Hom.: 945

Bravo AF: 0.391

Asia WGS AF: 0.387 AC: 1343 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.9
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10812641; hg19: chr9-2777384;