9-2838470-C-T

Position:

• chr9-2838470-C-T

Variant summary

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

The ENST00000397885.3(PUM3):​c.38G>A​(p.Ser13Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 1,612,134 control chromosomes in the GnomAD database, including 1,282 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.035 (104 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1178 hom.)
• Consequence: PUM3 ENST00000397885.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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 (MetaRNN=0.0013602376).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUM3	NM_014878.5	c.38G>A	p.Ser13Asn	missense_variant	2/18	ENST00000397885.3	NP_055693.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUM3	ENST00000397885.3	c.38G>A	p.Ser13Asn	missense_variant	2/18	1	NM_014878.5	ENSP00000380982	P1

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5328 AN: 152096 Hom.: 104 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0365

GnomAD3 exomes AF: 0.0404 AC: 10060 AN: 249140 Hom.: 225 AF XY: 0.0398 AC XY: 5378 AN XY: 135186

Gnomad AFR exome AF: 0.0241

Gnomad AMR exome AF: 0.0532

Gnomad ASJ exome AF: 0.0399

Gnomad EAS exome AF: 0.0545

Gnomad SAS exome AF: 0.0375

Gnomad FIN exome AF: 0.0404

Gnomad NFE exome AF: 0.0371

Gnomad OTH exome AF: 0.0427

GnomAD4 exome AF: 0.0373 AC: 54476 AN: 1459920 Hom.: 1178 Cov.: 30 AF XY: 0.0374 AC XY: 27133 AN XY: 726382

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.0527

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.0895

Gnomad4 SAS exome AF: 0.0354

Gnomad4 FIN exome AF: 0.0404

Gnomad4 NFE exome AF: 0.0352

Gnomad4 OTH exome AF: 0.0365

GnomAD4 genome AF: 0.0350 AC: 5333 AN: 152214 Hom.: 104 Cov.: 32 AF XY: 0.0343 AC XY: 2554 AN XY: 74420

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.0386

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.0629

Gnomad4 SAS AF: 0.0318

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.0375

Alfa AF: 0.0385 Hom.: 275

Bravo AF: 0.0355

TwinsUK AF: 0.0259 AC: 96

ALSPAC AF: 0.0311 AC: 120

ESP6500AA AF: 0.0260 AC: 96

ESP6500EA AF: 0.0411 AC: 337

ExAC AF: 0.0405 AC: 4898

Asia WGS AF: 0.0550 AC: 191 AN: 3478

EpiCase AF: 0.0381

EpiControl AF: 0.0371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.4
DANN	Benign	0.73
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.24
Sift	Benign	0.55	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.017
MPC		0.0036
ClinPred		0.00092	T
GERP RS		-1.5
Varity_R		0.031
gMVP		0.038

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: rs10968457; hg19: chr9-2838470; COSMIC: COSV67396428;