9-2804393-A-G

Variant names:

• chr9-2804393-A-G
• rs12171
• NM_014878.5:c.1885T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014878.5(PUM3):​c.1885T>C​(p.Leu629Leu) 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
• Publications: 8 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 -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.

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.1885T>C	p.Leu629Leu	synonymous	Exon 18 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.1885T>C	p.Leu629Leu	synonymous	Exon 18 of 18	ENSP00000380982.2	Q15397
	PUM3	ENST00000861029.1		c.2005T>C	p.Leu669Leu	synonymous	Exon 19 of 19	ENSP00000531088.1
	PUM3	ENST00000922208.1		c.2005T>C	p.Leu669Leu	synonymous	Exon 19 of 20	ENSP00000592267.1

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

GnomAD2 exomes AF: 0.0760 AC: 19085 AN: 251020 AF XY: 0.0724

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 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

African (AFR) AF: 0.192 AC: 6427 AN: 33438

American (AMR) AF: 0.137 AC: 6113 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 1250 AN: 26120

East Asian (EAS) AF: 0.0763 AC: 3027 AN: 39672

South Asian (SAS) AF: 0.0970 AC: 8354 AN: 86090

European-Finnish (FIN) AF: 0.0465 AC: 2480 AN: 53380

Middle Eastern (MID) AF: 0.0618 AC: 356 AN: 5764

European-Non Finnish (NFE) AF: 0.0488 AC: 54211 AN: 1111792

Other (OTH) AF: 0.0643 AC: 3882 AN: 60370

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

African (AFR) AF: 0.188 AC: 7807 AN: 41472

American (AMR) AF: 0.0931 AC: 1423 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0413 AC: 143 AN: 3466

East Asian (EAS) AF: 0.0559 AC: 289 AN: 5170

South Asian (SAS) AF: 0.0880 AC: 424 AN: 4820

European-Finnish (FIN) AF: 0.0442 AC: 468 AN: 10594

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0478 AC: 3250 AN: 68004

Other (OTH) AF: 0.0710 AC: 150 AN: 2114

Alfa AF: 0.0563 Hom.: 551

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.69
DANN	Benign	0.55
PhyloP100		0.18
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: rs12171; hg19: chr9-2804393; COSMIC: COSV65896629;