Genetic Variant UPF3A:c.208-5C>T (chr13-114282016-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001353645.1(UPF3A):c.-666C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000555 in 1,549,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

UPF3A
NM_001353645.1 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.0002463

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0200

Publications

0 publications found

Variant links:

Genes affected

UPF3A (HGNC:20332): (UPF3A regulator of nonsense mediated mRNA decay) This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. The encoded protein is one of two functional homologs to yeast Upf3p. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. It forms with Y14 a complex that binds specifically 20 nt upstream of exon-exon junctions. This gene is located on the long arm of chromosome 13. Several splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

UPF3A links:

ENSG00000289904 (HGNC:):

ENSG00000289904 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 13-114282016-C-T is Benign according to our data. Variant chr13-114282016-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644018.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353645.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UPF3A	NM_023011.4	MANE Select	c.208-5C>T	splice_region intron	N/A	NP_075387.1	Q9H1J1-1
UPF3A	NM_001353645.1		c.-666C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001340574.1	B3KUE7
UPF3A	NM_001353646.1		c.-302C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001340575.1	B3KUE7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UPF3A	ENST00000375299.8	TSL:1 MANE Select	c.208-5C>T	splice_region intron	N/A	ENSP00000364448.3	Q9H1J1-1
UPF3A	ENST00000351487.5	TSL:1	c.208-5C>T	splice_region intron	N/A	ENSP00000329592.5	Q9H1J1-2
UPF3A	ENST00000966313.1		c.208-5C>T	splice_region intron	N/A	ENSP00000636372.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000340

AC:

AN:

152866

AF XY:

0.000179

show subpopulations

Gnomad AFR exome

AF:

0.00519

Gnomad AMR exome

AF:

0.000271

Gnomad ASJ exome

AF:

0.000120

Gnomad EAS exome

AF:

0.0000844

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000849

Gnomad OTH exome

AF:

0.000233

GnomAD4 exome

AF:

0.0000551

AC:

AN:

1397606

Hom.:

Cov.:

AF XY:

0.0000493

AC XY:

AN XY:

690266

show subpopulations

African (AFR)

AF:

0.000189

AC:

AN:

31756

American (AMR)

AF:

0.000248

AC:

AN:

36356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25200

East Asian (EAS)

AF:

0.00

AC:

AN:

36148

South Asian (SAS)

AF:

0.0000377

AC:

AN:

79624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44508

Middle Eastern (MID)

AF:

0.00169

AC:

AN:

4722

European-Non Finnish (NFE)

AF:

0.0000407

AC:

AN:

1081338

Other (OTH)

AF:

0.000121

AC:

AN:

57954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41488

American (AMR)

AF:

0.000393

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67970

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000453

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.5

(source)

DANN

Benign

0.83

PhyloP100

0.020

PromoterAI

-0.050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00025

dbscSNV1_RF

Benign

0.0060

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over