9-2756638-C-T

Position:

• chr9-2756638-C-T

Variant summary

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

The ENST00000490444.2(PUM3):​c.*126+26118G>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,042 control chromosomes in the GnomAD database, including 46,159 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 0.78 (46159 hom., cov: 31)
• Consequence: PUM3 ENST00000490444.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUM3	ENST00000490444.2	c.*126+26118G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118040 AN: 151924 Hom.: 46139 Cov.: 31

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.777 AC: 118107 AN: 152042 Hom.: 46159 Cov.: 31 AF XY: 0.779 AC XY: 57871 AN XY: 74302

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.793

Alfa AF: 0.781 Hom.: 7167

Bravo AF: 0.771

Asia WGS AF: 0.823 AC: 2861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10967953; hg19: chr9-2756638;