NM_001020658.2:c.2994+735A>G

Variant names:

• chr1-30944611-T-C
• rs12406355
• NM_001020658.2:c.2994+735A>G

Variant summary

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

The NM_001020658.2(PUM1):​c.2994+735A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,080 control chromosomes in the GnomAD database, including 12,280 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 0.39 (12280 hom., cov: 32)
• Consequence: PUM1 NM_001020658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001020658.2. 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.2994+735A>G		intron	N/A	NP_001018494.1
	PUM1	NM_014676.3		c.2988+735A>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.2994+735A>G		intron	N/A	ENSP00000391723.2
	PUM1	ENST00000373741.8	TSL:1	c.3102+735A>G		intron	N/A	ENSP00000362846.4
	PUM1	ENST00000257075.9	TSL:1	c.2988+735A>G		intron	N/A	ENSP00000257075.5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59976 AN: 151962 Hom.: 12263 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.395 AC: 60032 AN: 152080 Hom.: 12280 Cov.: 32 AF XY: 0.399 AC XY: 29692 AN XY: 74344

African (AFR) AF: 0.328 AC: 13603 AN: 41504

American (AMR) AF: 0.461 AC: 7042 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3468

East Asian (EAS) AF: 0.339 AC: 1755 AN: 5172

South Asian (SAS) AF: 0.407 AC: 1964 AN: 4822

European-Finnish (FIN) AF: 0.499 AC: 5263 AN: 10552

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28085 AN: 67980

Other (OTH) AF: 0.376 AC: 793 AN: 2108

Alfa AF: 0.402 Hom.: 15985

Bravo AF: 0.386

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		0.13
Mutation Taster		=100/0	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: rs12406355; hg19: chr1-31417458;