9-2831891-T-C

Variant names:

• chr9-2831891-T-C
• rs10125846
• NM_014878.5:c.517-547A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014878.5(PUM3):​c.517-547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,002 control chromosomes in the GnomAD database, including 23,358 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 0.55 (23358 hom., cov: 32)
• Consequence: PUM3 NM_014878.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUM3	NM_014878.5	c.517-547A>G		intron_variant	Intron 5 of 17	ENST00000397885.3	NP_055693.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUM3	ENST00000397885.3	c.517-547A>G		intron_variant	Intron 5 of 17	1	NM_014878.5	ENSP00000380982.2

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83845 AN: 151884 Hom.: 23340 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.552 AC: 83914 AN: 152002 Hom.: 23358 Cov.: 32 AF XY: 0.554 AC XY: 41129 AN XY: 74286

African (AFR) AF: 0.553 AC: 22932 AN: 41434

American (AMR) AF: 0.514 AC: 7841 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2029 AN: 3466

East Asian (EAS) AF: 0.584 AC: 3022 AN: 5178

South Asian (SAS) AF: 0.616 AC: 2974 AN: 4826

European-Finnish (FIN) AF: 0.535 AC: 5653 AN: 10568

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37558 AN: 67944

Other (OTH) AF: 0.546 AC: 1154 AN: 2112

Alfa AF: 0.553 Hom.: 29015

Bravo AF: 0.550

Asia WGS AF: 0.574 AC: 1996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10125846; hg19: chr9-2831891;