NM_014878.5:c.866G>C

Variant names:

• chr9-2828765-C-G
• rs2173904
• NM_014878.5:c.866G>C

Variant summary

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

The NM_014878.5(PUM3):​c.866G>C​(p.Arg289Pro) variant causes a missense change. The variant allele was found at a frequency of 0.553 in 1,576,500 control chromosomes in the GnomAD database, including 243,751 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25298 hom., cov: 33)
  • Exomes 𝑓: 0.55 (218453 hom.)
• Consequence: PUM3 NM_014878.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.81
• Publications: 47 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 (MetaRNN=5.775965E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014878.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUM3	NM_014878.5	MANE Select	c.866G>C	p.Arg289Pro	missense	Exon 9 of 18	NP_055693.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUM3	ENST00000397885.3	TSL:1 MANE Select	c.866G>C	p.Arg289Pro	missense	Exon 9 of 18	ENSP00000380982.2	Q15397
	PUM3	ENST00000861029.1		c.986G>C	p.Arg329Pro	missense	Exon 10 of 19	ENSP00000531088.1
	PUM3	ENST00000922208.1		c.986G>C	p.Arg329Pro	missense	Exon 10 of 20	ENSP00000592267.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87198 AN: 151994 Hom.: 25254 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.565

GnomAD2 exomes AF: 0.558 AC: 139540 AN: 250236 AF XY: 0.560

Gnomad AFR exome AF: 0.631

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.589

Gnomad EAS exome AF: 0.590

Gnomad FIN exome AF: 0.535

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.572

GnomAD4 exome AF: 0.551 AC: 784773 AN: 1424388 Hom.: 218453 Cov.: 27 AF XY: 0.553 AC XY: 393470 AN XY: 711018

African (AFR) AF: 0.630 AC: 20536 AN: 32614

American (AMR) AF: 0.478 AC: 21259 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 15321 AN: 25866

East Asian (EAS) AF: 0.596 AC: 23529 AN: 39466

South Asian (SAS) AF: 0.608 AC: 51832 AN: 85240

European-Finnish (FIN) AF: 0.545 AC: 28997 AN: 53208

Middle Eastern (MID) AF: 0.638 AC: 3630 AN: 5694

European-Non Finnish (NFE) AF: 0.544 AC: 586460 AN: 1078714

Other (OTH) AF: 0.562 AC: 33209 AN: 59102

GnomAD4 genome AF: 0.574 AC: 87297 AN: 152112 Hom.: 25298 Cov.: 33 AF XY: 0.575 AC XY: 42786 AN XY: 74364

African (AFR) AF: 0.625 AC: 25948 AN: 41506

American (AMR) AF: 0.528 AC: 8077 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3466

East Asian (EAS) AF: 0.565 AC: 2928 AN: 5180

South Asian (SAS) AF: 0.613 AC: 2955 AN: 4822

European-Finnish (FIN) AF: 0.537 AC: 5672 AN: 10554

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37705 AN: 67978

Other (OTH) AF: 0.560 AC: 1184 AN: 2116

Alfa AF: 0.548 Hom.: 16231

Bravo AF: 0.575

TwinsUK AF: 0.545 AC: 2022

ALSPAC AF: 0.549 AC: 2116

ESP6500AA AF: 0.622 AC: 2737

ESP6500EA AF: 0.559 AC: 4808

ExAC AF: 0.566 AC: 68718

Asia WGS AF: 0.567 AC: 1970 AN: 3476

EpiCase AF: 0.557

EpiControl AF: 0.552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	19
DANN	Benign	0.23
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.033	T
MetaRNN	Benign	0.000058	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.055
Sift	Benign	0.70	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.051
MPC		0.0028
ClinPred		0.016	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.59
Mutation Taster		=89/11	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2173904; hg19: chr9-2828765; COSMIC: COSV67395713;