rs587782926

Variant names:

• chr15-25339119-ATTTTGTTTTGTTTTG-A
• rs587782926
• NM_130839.5:c.*3_*17delCAAAACAAAACAAAA

Your query was ambiguous. Multiple possible variants found:

• chr15-25339119-ATTTTGTTTTGTTTTG-A
• chr15-25339119-ATTTTGTTTTGTTTTG-ATTTTG
• chr15-25339119-ATTTTGTTTTGTTTTG-ATTTTGTTTTG
• chr15-25339119-ATTTTGTTTTGTTTTG-ATTTTGTTTTGTTTTGTTTTG
• chr15-25339119-ATTTTGTTTTGTTTTG-ATTTTGTTTTGTTTTGTTTTGTTTTG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_130839.5(UBE3A):​c.*3_*17delCAAAACAAAACAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 1,429,944 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000073 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: UBE3A NM_130839.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.720
• Publications: 0 publications found

Genes affected

UBE3A (HGNC:12496): (ubiquitin protein ligase E3A) This gene encodes an E3 ubiquitin-protein ligase, part of the ubiquitin protein degradation system. This imprinted gene is maternally expressed in brain and biallelically expressed in other tissues. Maternally inherited deletion of this gene causes Angelman Syndrome, characterized by severe motor and intellectual retardation, ataxia, hypotonia, epilepsy, absence of speech, and characteristic facies. The protein also interacts with the E6 protein of human papillomavirus types 16 and 18, resulting in ubiquitination and proteolysis of tumor protein p53. Alternative splicing of this gene results in three transcript variants encoding three isoforms with different N-termini. Additional transcript variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

SNHG14 (HGNC:37462): (small nucleolar RNA host gene 14) This gene is located within the Prader-Willi critical region and produces a long, spliced paternally-imprinted RNA that initiates within a common upstream promoter region shared by the SNRPN (small nuclear ribonucleoprotein polypeptide N) and SNURF genes. This transcript serves as a host RNA for the small nucleolar RNA, C/D box 115 and 116 clusters. This RNA extends in antisense into the region of the ubiquitin protein ligase E3A gene (UBE3A), and is thought to regulate imprinted expression of UBE3A in the brain. This transcript undergoes extensive alternative splicing, and may initiate and terminate at multiple locations within this genomic region. The full-length structure of all splice forms is not determined. [provided by RefSeq, Mar 2017]

ACMG classification

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

• BP6: Variant 15-25339119-ATTTTGTTTTGTTTTG-A is Benign according to our data. Variant chr15-25339119-ATTTTGTTTTGTTTTG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1201398.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130839.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3A	NM_130839.5	MANE Select	c.*3_*17delCAAAACAAAACAAAA		3_prime_UTR	Exon 13 of 13	NP_570854.1	Q05086-3
	UBE3A	NM_000462.5		c.*3_*17delCAAAACAAAACAAAA		3_prime_UTR	Exon 14 of 14	NP_000453.2
	UBE3A	NM_001354505.1		c.*3_*17delCAAAACAAAACAAAA		3_prime_UTR	Exon 13 of 13	NP_001341434.1	Q05086-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE3A	ENST00000648336.2	MANE Select	c.*3_*17delCAAAACAAAACAAAA		3_prime_UTR	Exon 13 of 13	ENSP00000497572.2	Q05086-3
	UBE3A	ENST00000566215.5	TSL:1	c.*3_*17delCAAAACAAAACAAAA		3_prime_UTR	Exon 15 of 15	ENSP00000457771.1	Q05086-2
	SNHG14	ENST00000424333.6	TSL:1	n.5766+60240_5766+60254delGTTTTGTTTTGTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000731 AC: 1 AN: 136802 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000162

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 8 AN: 1293142 Hom.: 0 AF XY: 0.00000948 AC XY: 6 AN XY: 632782

African (AFR) AF: 0.00 AC: 0 AN: 27556

American (AMR) AF: 0.0000440 AC: 1 AN: 22732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21018

East Asian (EAS) AF: 0.00 AC: 0 AN: 34130

South Asian (SAS) AF: 0.00 AC: 0 AN: 59102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4008

European-Non Finnish (NFE) AF: 0.00000584 AC: 6 AN: 1027616

Other (OTH) AF: 0.0000190 AC: 1 AN: 52588

GnomAD4 genome AF: 0.00000731 AC: 1 AN: 136802 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 66620

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 36742

American (AMR) AF: 0.00 AC: 0 AN: 13946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3202

East Asian (EAS) AF: 0.00 AC: 0 AN: 4744

South Asian (SAS) AF: 0.00 AC: 0 AN: 4364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000162 AC: 1 AN: 61914

Other (OTH) AF: 0.00 AC: 0 AN: 1900

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72

Splicing

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

Other links and lift over

dbSNP: rs587782926; hg19: chr15-25584266;