Genetic Variant PUM1:c.3435+1434A>G (chr1-30935209-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001020658.2(PUM1):c.3435+1434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,212 control chromosomes in the GnomAD database, including 46,404 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 0.77 ( 46404 hom., cov: 32)

Consequence

PUM1
NM_001020658.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.202

Publications

4 publications found

Variant links:

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

PUM1 links:

ENSG00000307336 (HGNC:):

ENSG00000307336 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUM1	NM_001020658.2 link	c.3435+1434A>G		intron_variant	Intron 21 of 21	ENST00000426105.7	NP_001018494.1
PUM1	NM_014676.3 link	c.3429+1434A>G		intron_variant	Intron 21 of 21		NP_055491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUM1	ENST00000426105.7 link	c.3435+1434A>G		intron_variant	Intron 21 of 21	1	NM_001020658.2	ENSP00000391723.2

Frequencies

GnomAD3 genomes

AF:

0.773

AC:

117519

AN:

152094

Hom.:

46341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.918

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.873

Gnomad SAS

AF:

0.897

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.696

Gnomad OTH

AF:

0.711

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

GnomAD4 genome

AF:

0.773

AC:

117638

AN:

152212

Hom.:

46404

Cov.:

AF XY:

0.778

AC XY:

57924

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.918

AC:

38139

AN:

41552

American (AMR)

AF:

0.689

AC:

10531

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

2119

AN:

3472

East Asian (EAS)

AF:

0.873

AC:

4516

AN:

5174

South Asian (SAS)

AF:

0.897

AC:

4327

AN:

4824

European-Finnish (FIN)

AF:

0.795

AC:

8433

AN:

10606

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.696

AC:

47342

AN:

67988

Other (OTH)

AF:

0.715

AC:

1508

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1330

2661

3991

5322

6652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.715

Hom.:

114047

Bravo

AF:

0.763

Asia WGS

AF:

0.871

AC:

3029

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.8

(source)

DANN

Benign

0.57

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over