chr15-24829812-T-C

Position:

• chr15-24829812-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000400100.5(SNRPN):​c.-672T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,978 control chromosomes in the GnomAD database, including 1,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1751 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: SNRPN ENST00000400100.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69

Genes affected

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]

SNHG14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 15-24829812-T-C is Benign according to our data. Variant chr15-24829812-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 315431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNHG14	NR_146177.1	n.231T>C		non_coding_transcript_exon_variant	2/148

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRPN	ENST00000400100.5	c.-672T>C		5_prime_UTR_variant	2/13	1		ENSP00000382972	P1
SNRPN	ENST00000642807.1	c.-860T>C		5_prime_UTR_variant	2/14			ENSP00000495345	P1
SNRPN	ENST00000645002.1	c.-971T>C		5_prime_UTR_variant	2/15			ENSP00000494831	P1
SNRPN	ENST00000400098.6	n.187+5989T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20883 AN: 151812 Hom.: 1735 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.146 AC: 7 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.156 AC XY: 5 AN XY: 32

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.138 AC: 20924 AN: 151930 Hom.: 1751 Cov.: 32 AF XY: 0.138 AC XY: 10208 AN XY: 74234

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0273

Gnomad4 SAS AF: 0.0527

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.127

Alfa AF: 0.126 Hom.: 164

Bravo AF: 0.139

Asia WGS AF: 0.0550 AC: 195 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Autism spectrum disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs7170796; hg19: chr15-25074959;