rs7879933

Variant names:

• chrX-119583024-C-A
• rs7879933
• NM_003336.4:c.331-103C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003336.4(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 NM_003336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 2 publications found

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]

UBE2A Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability Nascimento type

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003336.4. 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
	UBE2A	NM_003336.4	MANE Select	c.331-103C>A		intron	N/A	NP_003327.2
	UBE2A	NM_181762.3		c.241-103C>A		intron	N/A	NP_861427.1	P49459-2
	UBE2A	NM_001282161.2		c.232-103C>A		intron	N/A	NP_001269090.1	A0A0D9SG71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2A	ENST00000371558.7	TSL:1 MANE Select	c.331-103C>A		intron	N/A	ENSP00000360613.2	P49459-1
	UBE2A	ENST00000371569.6	TSL:1	n.1352-103C>A		intron	N/A
	UBE2A	ENST00000696533.1		c.547-103C>A		intron	N/A	ENSP00000512694.1	A0A8Q3SIL6

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 4834 AN: 110615 Hom.: 94 Cov.: 22

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

African (AFR) AF: 0.0626 AC: 1449 AN: 23137

American (AMR) AF: 0.0144 AC: 485 AN: 33604

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 578 AN: 17817

East Asian (EAS) AF: 0.000345 AC: 10 AN: 28991

South Asian (SAS) AF: 0.0915 AC: 4473 AN: 48904

European-Finnish (FIN) AF: 0.0547 AC: 1899 AN: 34742

Middle Eastern (MID) AF: 0.0770 AC: 268 AN: 3479

European-Non Finnish (NFE) AF: 0.0428 AC: 30110 AN: 703270

Other (OTH) AF: 0.0455 AC: 1847 AN: 40562

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

African (AFR) AF: 0.0571 AC: 1741 AN: 30496

American (AMR) AF: 0.0227 AC: 236 AN: 10392

Ashkenazi Jewish (ASJ) AF: 0.0319 AC: 84 AN: 2636

East Asian (EAS) AF: 0.00198 AC: 7 AN: 3536

South Asian (SAS) AF: 0.0921 AC: 243 AN: 2638

European-Finnish (FIN) AF: 0.0495 AC: 279 AN: 5639

Middle Eastern (MID) AF: 0.0708 AC: 15 AN: 212

European-Non Finnish (NFE) AF: 0.0412 AC: 2181 AN: 52897

Other (OTH) AF: 0.0359 AC: 54 AN: 1506

Alfa AF: 0.0446 Hom.: 2781

Bravo AF: 0.0415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.67
PhyloP100		-0.080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7879933; hg19: chrX-118716987;