rs769335743

Variant names:

• chrX-119560352-C-A
• rs769335743
• NM_022101.4:c.158G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-119560352-C-A
• chrX-119560352-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022101.4(STEEP1):​c.158G>T​(p.Arg53Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: STEEP1 NM_022101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28
• Publications: 0 publications found

Genes affected

STEEP1 (HGNC:26239): (STING1 ER exit protein 1) While this gene is well-supported by transcript data, no functional information on its protein products is currently available. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022101.4. 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
	STEEP1	NM_022101.4	MANE Select	c.158G>T	p.Arg53Leu	missense	Exon 2 of 7	NP_071384.1	Q9H5V9-1
	STEEP1	NM_001170570.2		c.158G>T	p.Arg53Leu	missense	Exon 2 of 6	NP_001164041.1	Q9H5V9-3
	STEEP1	NM_001170569.1		c.11G>T	p.Arg4Leu	missense	Exon 2 of 7	NP_001164040.1	Q9H5V9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEEP1	ENST00000644802.2	MANE Select	c.158G>T	p.Arg53Leu	missense	Exon 2 of 7	ENSP00000494123.2	Q9H5V9-1
	STEEP1	ENST00000868973.1		c.158G>T	p.Arg53Leu	missense	Exon 2 of 8	ENSP00000539032.1
	STEEP1	ENST00000536133.2	TSL:2	c.158G>T	p.Arg53Leu	missense	Exon 2 of 6	ENSP00000441786.1	Q9H5V9-3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.13e-7 AC: 1 AN: 1095642 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 361032

African (AFR) AF: 0.00 AC: 0 AN: 26349

American (AMR) AF: 0.00 AC: 0 AN: 35171

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19366

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.00 AC: 0 AN: 54031

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839883

Other (OTH) AF: 0.0000217 AC: 1 AN: 46004

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Intellectual disability, X-linked 107 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.22	N
PhyloP100		5.3
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.22
Sift	Benign	0.17	T
Sift4G	Benign	0.42	T
Polyphen		0.0010	B
Vest4		0.48
MutPred		0.33		Loss of MoRF binding (P = 0.0142)
MVP		0.81
ClinPred		0.83	D
GERP RS		4.7
Varity_R		0.51
gMVP		0.94
Mutation Taster		=33/67	disease causing

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: rs769335743; hg19: chrX-118694315;