1-31030844-G-C

Variant names:

• chr1-31030844-G-C
• rs4949332
• NM_001020658.2:c.364-1980C>G

Variant summary

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

The ENST00000426105.7(PUM1):​c.364-1980C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,140 control chromosomes in the GnomAD database, including 37,569 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 0.69 (37569 hom., cov: 33)
• Consequence: PUM1 ENST00000426105.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.96
• Publications: 2 publications found

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]

PUM1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• spinocerebellar ataxia 47

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000426105.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUM1	NM_001020658.2	MANE Select	c.364-1980C>G		intron	N/A	NP_001018494.1
	PUM1	NM_014676.3		c.364-1980C>G		intron	N/A	NP_055491.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUM1	ENST00000426105.7	TSL:1 MANE Select	c.364-1980C>G		intron	N/A	ENSP00000391723.2
	PUM1	ENST00000373741.8	TSL:1	c.472-1980C>G		intron	N/A	ENSP00000362846.4
	PUM1	ENST00000257075.9	TSL:1	c.364-1980C>G		intron	N/A	ENSP00000257075.5

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104761 AN: 152022 Hom.: 37521 Cov.: 33

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.625

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.689 AC: 104861 AN: 152140 Hom.: 37569 Cov.: 33 AF XY: 0.694 AC XY: 51645 AN XY: 74384

African (AFR) AF: 0.868 AC: 36041 AN: 41530

American (AMR) AF: 0.627 AC: 9575 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1688 AN: 3466

East Asian (EAS) AF: 0.872 AC: 4521 AN: 5184

South Asian (SAS) AF: 0.742 AC: 3577 AN: 4824

European-Finnish (FIN) AF: 0.709 AC: 7492 AN: 10566

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40041 AN: 67988

Other (OTH) AF: 0.629 AC: 1328 AN: 2110

Alfa AF: 0.645 Hom.: 4023

Bravo AF: 0.686

Asia WGS AF: 0.788 AC: 2742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.085
DANN	Benign	0.37
PhyloP100		-4.0
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: rs4949332; hg19: chr1-31503691;