rs7879933

Positions:

• chrX-119583024-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000371558.7(UBE2A):​c.331-103C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 1,045,144 control chromosomes in the GnomAD database, including 812 homozygotes. There are 13,972 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.044 (95 hom., 1380 hem., cov: 22)
  • Exomes 𝑓: 0.044 (717 hom. 12592 hem.)
• Consequence: UBE2A ENST00000371558.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

Genes affected

UBE2A (HGNC:12472): (ubiquitin conjugating enzyme E2 A) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, ubiquitin-conjugating enzymes, and ubiquitin-protein ligases. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is required for post-replicative DNA damage repair, and may play a role in transcriptional regulation. Mutations in this gene are associated with cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2A	NM_003336.4	c.331-103C>A		intron_variant		ENST00000371558.7	NP_003327.2
UBE2A	NM_001282161.2	c.232-103C>A		intron_variant			NP_001269090.1
UBE2A	NM_181762.3	c.241-103C>A		intron_variant			NP_861427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2A	ENST00000371558.7	c.331-103C>A		intron_variant		1	NM_003336.4	ENSP00000360613	P4

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 4834 AN: 110615 Hom.: 94 Cov.: 22 AF XY: 0.0417 AC XY: 1375 AN XY: 32967

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0319

Gnomad EAS AF: 0.00197

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.0681

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.0362

GnomAD4 exome AF: 0.0440 AC: 41119 AN: 934506 Hom.: 717 AF XY: 0.0481 AC XY: 12592 AN XY: 261836

Gnomad4 AFR exome AF: 0.0626

Gnomad4 AMR exome AF: 0.0144

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.000345

Gnomad4 SAS exome AF: 0.0915

Gnomad4 FIN exome AF: 0.0547

Gnomad4 NFE exome AF: 0.0428

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0437 AC: 4840 AN: 110638 Hom.: 95 Cov.: 22 AF XY: 0.0418 AC XY: 1380 AN XY: 33004

Gnomad4 AFR AF: 0.0571

Gnomad4 AMR AF: 0.0227

Gnomad4 ASJ AF: 0.0319

Gnomad4 EAS AF: 0.00198

Gnomad4 SAS AF: 0.0921

Gnomad4 FIN AF: 0.0495

Gnomad4 NFE AF: 0.0412

Gnomad4 OTH AF: 0.0359

Alfa AF: 0.0442 Hom.: 2023

Bravo AF: 0.0415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.67

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: rs7879933; hg19: chrX-118716987;