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GeneBe

15-24962126-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_001394334.1(SNURF):c.27C>T(p.His9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,614,098 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0095 ( 19 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 29 hom. )

Consequence

SNURF
NM_001394334.1 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.546
Variant links:
Genes affected
SNURF (HGNC:11171): (SNRPN upstream open reading frame) This gene is located within the Prader-Willi Syndrome critical region on chromosome 15. Transcripts produced from this gene initiate at an imprinting center and are paternally-imprinted. These transcripts may be bicistronic and also encode SNRPN (small nuclear ribonucleoprotein polypeptide N) from a downstream open reading frame. The small protein represented by this gene is encoded by an evolutionarily-conserved upstream open reading frame and is localized to the nucleus. Extensive alternative splicing and promoter usage occurs in this region and the full-length nature of some of these transcripts has not been determined. Alterations in the imprinting center are associated with parental imprint switch failure, which may cause Angelman syndrome or Prader-Willi syndrome. [provided by RefSeq, Mar 2017]
SNRPN (HGNC:11164): (small nuclear ribonucleoprotein polypeptide N) This gene is located within the Prader-Willi Syndrome critical region on chromosome 15 and is imprinted and expressed from the paternal allele. It encodes a component of the small nuclear ribonucleoprotein complex, which functions in pre-mRNA processing and may contribute to tissue-specific alternative splicing. Alternative promoter use and alternative splicing result in a multitude of transcript variants encoding the same protein. Transcript variants that initiate at the CpG island-associated imprinting center may be bicistronic and also encode the SNRPN upstream reading frame protein (SNURF) from an upstream open reading frame. In addition, long spliced transcripts for small nucleolar RNA host gene 14 (SNHG14) may originate from the promoters at this locus and share exons with this gene. Alterations in this region are associated with parental imprint switch failure, which may cause Angelman syndrome or Prader-Willi syndrome. [provided by RefSeq, Mar 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-24962126-C-T is Benign according to our data. Variant chr15-24962126-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 315440.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.546 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00952 (1449/152278) while in subpopulation AFR AF= 0.0322 (1338/41552). AF 95% confidence interval is 0.0308. There are 19 homozygotes in gnomad4. There are 648 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 19 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNURFNM_001394334.1 linkuse as main transcriptc.27C>T p.His9= synonymous_variant 2/3 ENST00000577949.6
SNRPNNM_003097.6 linkuse as main transcriptc.-378C>T 5_prime_UTR_variant 2/10 ENST00000390687.9
SNHG14NR_146177.1 linkuse as main transcriptn.525C>T non_coding_transcript_exon_variant 5/148

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNURFENST00000577949.6 linkuse as main transcriptc.27C>T p.His9= synonymous_variant 2/32 NM_001394334.1 P1
SNRPNENST00000390687.9 linkuse as main transcriptc.-378C>T 5_prime_UTR_variant 2/101 NM_003097.6 P1P63162-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00950
AC:
1445
AN:
152160
Hom.:
19
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0322
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00249
Gnomad ASJ
AF:
0.0101
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00622
GnomAD3 exomes
AF:
0.00320
AC:
798
AN:
249016
Hom.:
16
AF XY:
0.00234
AC XY:
316
AN XY:
134806
show subpopulations
Gnomad AFR exome
AF:
0.0345
Gnomad AMR exome
AF:
0.00217
Gnomad ASJ exome
AF:
0.00904
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000503
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00143
AC:
2087
AN:
1461820
Hom.:
29
Cov.:
31
AF XY:
0.00126
AC XY:
914
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.0354
Gnomad4 AMR exome
AF:
0.00235
Gnomad4 ASJ exome
AF:
0.00872
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000300
Gnomad4 OTH exome
AF:
0.00361
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00952
AC:
1449
AN:
152278
Hom.:
19
Cov.:
32
AF XY:
0.00870
AC XY:
648
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0322
Gnomad4 AMR
AF:
0.00249
Gnomad4 ASJ
AF:
0.0101
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00530
Hom.:
10
Bravo
AF:
0.0113
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000654
EpiControl
AF:
0.000711

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Autism spectrum disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
7.7
Dann
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs426541; hg19: chr15-25207273; API