rs2270891

Variant names:

• chr9-2828742-C-A
• rs2270891
• NM_014878.5:c.889G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-2828742-C-A
• chr9-2828742-C-T

Variant summary

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

The NM_014878.5(PUM3):​c.889G>T​(p.Val297Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,605,370 control chromosomes in the GnomAD database, including 1,348 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.043 (152 hom., cov: 33)
  • Exomes 𝑓: 0.037 (1196 hom.)
• Consequence: PUM3 NM_014878.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.734
• Publications: 15 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=0.0017007887).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0654 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.889G>T	p.Val297Leu	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.889G>T	p.Val297Leu	missense	Exon 9 of 18	ENSP00000380982.2	Q15397
	PUM3	ENST00000861029.1		c.1009G>T	p.Val337Leu	missense	Exon 10 of 19	ENSP00000531088.1
	PUM3	ENST00000922208.1		c.1009G>T	p.Val337Leu	missense	Exon 10 of 20	ENSP00000592267.1

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6488 AN: 152154 Hom.: 152 Cov.: 33

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0426 AC: 10687 AN: 250982 AF XY: 0.0411

Gnomad AFR exome AF: 0.0512

Gnomad AMR exome AF: 0.0557

Gnomad ASJ exome AF: 0.0387

Gnomad EAS exome AF: 0.0604

Gnomad FIN exome AF: 0.0402

Gnomad NFE exome AF: 0.0365

Gnomad OTH exome AF: 0.0435

GnomAD4 exome AF: 0.0373 AC: 54180 AN: 1453098 Hom.: 1196 Cov.: 28 AF XY: 0.0373 AC XY: 26982 AN XY: 723512

African (AFR) AF: 0.0474 AC: 1575 AN: 33238

American (AMR) AF: 0.0548 AC: 2446 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.0379 AC: 987 AN: 26050

East Asian (EAS) AF: 0.101 AC: 3989 AN: 39584

South Asian (SAS) AF: 0.0355 AC: 3051 AN: 86010

European-Finnish (FIN) AF: 0.0402 AC: 2147 AN: 53344

Middle Eastern (MID) AF: 0.0475 AC: 272 AN: 5730

European-Non Finnish (NFE) AF: 0.0339 AC: 37461 AN: 1104462

Other (OTH) AF: 0.0375 AC: 2252 AN: 60052

GnomAD4 genome AF: 0.0426 AC: 6491 AN: 152272 Hom.: 152 Cov.: 33 AF XY: 0.0420 AC XY: 3128 AN XY: 74456

African (AFR) AF: 0.0514 AC: 2138 AN: 41556

American (AMR) AF: 0.0406 AC: 621 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3470

East Asian (EAS) AF: 0.0713 AC: 370 AN: 5186

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4822

European-Finnish (FIN) AF: 0.0383 AC: 406 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0370 AC: 2517 AN: 68026

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0392 Hom.: 491

Bravo AF: 0.0439

TwinsUK AF: 0.0264 AC: 98

ALSPAC AF: 0.0317 AC: 122

ESP6500AA AF: 0.0495 AC: 218

ESP6500EA AF: 0.0397 AC: 341

ExAC AF: 0.0431 AC: 5231

Asia WGS AF: 0.0600 AC: 210 AN: 3478

EpiCase AF: 0.0384

EpiControl AF: 0.0366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.96
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.73
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.060
Sift	Benign	0.34	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.097		Loss of ubiquitination at K293 (P = 0.0834)
MPC		0.0035
ClinPred		0.0013	T
GERP RS		0.67
Varity_R		0.075
gMVP		0.39
Mutation Taster		=91/9	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: rs2270891; hg19: chr9-2828742; COSMIC: COSV67396424;