Genetic Variant STEEP1:p.Glu167_Glu168del (chrX-119542514-CTCCTCT-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate

The NM_022101.4(STEEP1):c.498_503delAGAGGA(p.Glu167_Glu168del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

STEEP1
NM_022101.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.11

Publications

0 publications found

Variant links:

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]

STEEP1 links:

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)

UBE2A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_022101.4.

PP5

Variant X-119542514-CTCCTCT-C is Pathogenic according to our data. Variant chrX-119542514-CTCCTCT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 976767.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEEP1	NM_022101.4	MANE Select	c.498_503delAGAGGA	p.Glu167_Glu168del	disruptive_inframe_deletion	Exon 5 of 7	NP_071384.1	Q9H5V9-1
STEEP1	NM_001170570.2		c.456_461delAGAGGA	p.Glu153_Glu154del	disruptive_inframe_deletion	Exon 4 of 6	NP_001164041.1	Q9H5V9-3
STEEP1	NM_001170569.1		c.351_356delAGAGGA	p.Glu118_Glu119del	disruptive_inframe_deletion	Exon 5 of 7	NP_001164040.1	Q9H5V9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEEP1	ENST00000644802.2	MANE Select	c.498_503delAGAGGA	p.Glu167_Glu168del	disruptive_inframe_deletion	Exon 5 of 7	ENSP00000494123.2	Q9H5V9-1
STEEP1	ENST00000868973.1		c.498_503delAGAGGA	p.Glu167_Glu168del	disruptive_inframe_deletion	Exon 5 of 8	ENSP00000539032.1
STEEP1	ENST00000536133.2	TSL:2	c.456_461delAGAGGA	p.Glu153_Glu154del	disruptive_inframe_deletion	Exon 4 of 6	ENSP00000441786.1	Q9H5V9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1088617

Hom.:

AF XY:

0.00

AC XY:

AN XY:

354413

African (AFR)

AF:

0.00

AC:

AN:

26213

American (AMR)

AF:

0.00

AC:

AN:

35137

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19321

East Asian (EAS)

AF:

0.00

AC:

AN:

30128

South Asian (SAS)

AF:

0.00

AC:

AN:

53809

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40517

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

833606

Other (OTH)

AF:

0.00

AC:

AN:

45774

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual disability, X-linked 107 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.1

Mutation Taster

=13/187

disease causing (ClinVar)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over