1-30941125-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001020658.2(PUM1):c.3242+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,596,186 control chromosomes in the GnomAD database, including 7,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (678 hom., cov: 32)
  • Exomes 𝑓: 0.080 (6789 hom.)
• Consequence: PUM1 NM_001020658.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.04

Genes affected

PUM1 (HGNC:14957): (pumilio RNA binding family member 1) This gene encodes a member of the PUF family, evolutionarily conserved RNA-binding proteins related to the Pumilio proteins of Drosophila and the fem-3 mRNA binding factor proteins of C. elegans. The encoded protein contains a sequence-specific RNA binding domain comprised of eight repeats and N- and C-terminal flanking regions, and serves as a translational regulator of specific mRNAs by binding to their 3' untranslated regions. The evolutionarily conserved function of the encoded protein in invertebrates and lower vertebrates suggests that the human protein may be involved in translational regulation of embryogenesis, and cell development and differentiation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-30941125-T-C is Benign according to our data. Variant chr1-30941125-T-C is described in ClinVar as [Benign]. Clinvar id is 1237249.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUM1	NM_001020658.2	c.3242+26A>G		intron_variant		ENST00000426105.7
PUM1	NM_014676.3	c.3236+26A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUM1	ENST00000426105.7	c.3242+26A>G		intron_variant		1	NM_001020658.2	A1

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11186 AN: 152156 Hom.: 681 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0660

GnomAD3 exomes AF: 0.111 AC: 27370 AN: 246742 Hom.: 2240 AF XY: 0.111 AC XY: 14834 AN XY: 133324

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.0577

Gnomad EAS exome AF: 0.282

Gnomad SAS exome AF: 0.166

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.0657

Gnomad OTH exome AF: 0.0933

GnomAD4 exome AF: 0.0800 AC: 115563 AN: 1443912 Hom.: 6789 Cov.: 30 AF XY: 0.0832 AC XY: 59746 AN XY: 718316

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.0589

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.0622

Gnomad4 OTH exome AF: 0.0841

GnomAD4 genome AF: 0.0734 AC: 11181 AN: 152274 Hom.: 678 Cov.: 32 AF XY: 0.0805 AC XY: 5994 AN XY: 74450

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0659

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0686 Hom.: 840

Bravo AF: 0.0676

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.019
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3795433; hg19: chr1-31413972; COSMIC: COSV57083249; COSMIC: COSV57083249;