9-2804393-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014878.5(PUM3):c.1885T>C(p.Leu629=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 1,613,394 control chromosomes in the GnomAD database, including 4,311 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 0.092 (993 hom., cov: 32)
  • Exomes 𝑓: 0.059 (3318 hom.)
• Consequence: PUM3 NM_014878.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUM3	NM_014878.5	c.1885T>C	p.Leu629=	synonymous_variant	18/18	ENST00000397885.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUM3	ENST00000397885.3	c.1885T>C	p.Leu629=	synonymous_variant	18/18	1	NM_014878.5	P1
PUM3	ENST00000382032.3	n.232T>C		non_coding_transcript_exon_variant	2/2	2
PUM3	ENST00000490444.2	c.88T>C	p.Leu30=	synonymous_variant, NMD_transcript_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14028 AN: 152018 Hom.: 995 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.0413

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0717

GnomAD3 exomes AF: 0.0760 AC: 19085 AN: 251020 Hom.: 1103 AF XY: 0.0724 AC XY: 9827 AN XY: 135690

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.0459

Gnomad EAS exome AF: 0.0477

Gnomad SAS exome AF: 0.0954

Gnomad FIN exome AF: 0.0457

Gnomad NFE exome AF: 0.0479

Gnomad OTH exome AF: 0.0650

GnomAD4 exome AF: 0.0589 AC: 86100 AN: 1461258 Hom.: 3318 Cov.: 31 AF XY: 0.0592 AC XY: 43052 AN XY: 726902

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.0479

Gnomad4 EAS exome AF: 0.0763

Gnomad4 SAS exome AF: 0.0970

Gnomad4 FIN exome AF: 0.0465

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0643

GnomAD4 genome AF: 0.0922 AC: 14026 AN: 152136 Hom.: 993 Cov.: 32 AF XY: 0.0903 AC XY: 6720 AN XY: 74396

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0931

Gnomad4 ASJ AF: 0.0413

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0514 Hom.: 358

Bravo AF: 0.102

Asia WGS AF: 0.0920 AC: 317 AN: 3478

EpiCase AF: 0.0491

EpiControl AF: 0.0490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.69
Dann	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs12171; hg19: chr9-2804393; COSMIC: COSV65896629;