rs7857841

Positions:

• chr9-2756756-A-C
• chr9-2756756-A-G
• chr9-2756756-A-T

Variant summary

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

The ENST00000490444.2(PUM3):​c.*126+26000T>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,154 control chromosomes in the GnomAD database, including 59,650 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 0.88 (59650 hom., cov: 31)
• Consequence: PUM3 ENST00000490444.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 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+26000T>G		intron_variant, NMD_transcript_variant		5		ENSP00000474467

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134438 AN: 152036 Hom.: 59598 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.885

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

GnomAD4 genome AF: 0.884 AC: 134550 AN: 152154 Hom.: 59650 Cov.: 31 AF XY: 0.886 AC XY: 65897 AN XY: 74386

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.884

Alfa AF: 0.898 Hom.: 58361

Bravo AF: 0.883

Asia WGS AF: 0.918 AC: 3190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7857841; hg19: chr9-2756756;