rs4949332

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-31030844-G-A
• chr1-31030844-G-C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACMG Germline Pathogenicity v2019). BP4_Strong

The NM_001020658.2(PUM1):c.364-1980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. No reliable population frequency data is available for this variant in the gnomAD database. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PUM1 NM_001020658.2 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: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia
• spinocerebellar ataxia 47

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

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001020658.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PUM1 NM_001020658.2	MANE Select	c.364-1980C>T	intron	Intron 2 of 21	Prot: NP_001018494.1 UniProt:
	PUM1 NM_014676.3		c.364-1980C>T	intron	Intron 2 of 21	Prot: NP_055491.1 UniProt:

PUM1 NM_001020658.2

MANE Select

HGVSc / HGVSpc.364-1980C>T

Exon rankIntron 2 of 21

intron

Prot: NP_001018494.1UniProt: Q14671-3

PUM1 NM_014676.3

HGVSc / HGVSpc.364-1980C>T

Exon rankIntron 2 of 21

intron

Prot: NP_055491.1UniProt: Q14671-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PUM1 ENST00000426105.7	TSL:1MANE Select	c.364-1980C>T	intron	Intron 2 of 21	Prot: ENSP00000391723.2 UniProt:
	PUM1 ENST00000373741.8	TSL:1	c.472-1980C>T	intron	Intron 2 of 21	Prot: ENSP00000362846.4 UniProt:
	PUM1 ENST00000257075.9	TSL:1	c.364-1980C>T	intron	Intron 2 of 21	Prot: ENSP00000257075.5 UniProt:

PUM1 ENST00000426105.7

TSL:1MANE Select

HGVSc / HGVSpc.364-1980C>T

Exon rankIntron 2 of 21

intron

Prot: ENSP00000391723.2UniProt: Q14671-3

PUM1 ENST00000373741.8

TSL:1

HGVSc / HGVSpc.472-1980C>T

Exon rankIntron 2 of 21

intron

Prot: ENSP00000362846.4UniProt: Q5T1Z8

PUM1 ENST00000257075.9

TSL:1

HGVSc / HGVSpc.364-1980C>T

Exon rankIntron 2 of 21

intron

Prot: ENSP00000257075.5UniProt: Q14671-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00	AC:0	Hom:0	AN:152062	Cov:33
GnomAD4 genome Warning	AF: 0.00	AC:0	Hom:0	AN:152062	Cov:33

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.32
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.92
GPN-Star LLR	N/A	0.29
GPN-Star score	N/A	0.26
PhyloP100	Benign	-4.0

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs4949332;

hg19: chr1-31503691;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar