X-119560341-G-C

Position:

• chrX-119560341-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022101.4(STEEP1):​c.169C>G​(p.Arg57Gly) 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)
• Consequence: STEEP1 NM_022101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEEP1	NM_022101.4	c.169C>G	p.Arg57Gly	missense_variant	2/7	ENST00000644802.2	NP_071384.1
STEEP1	NM_001170570.2	c.169C>G	p.Arg57Gly	missense_variant	2/6		NP_001164041.1
STEEP1	NM_001170569.1	c.22C>G	p.Arg8Gly	missense_variant	2/7		NP_001164040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEEP1	ENST00000644802.2	c.169C>G	p.Arg57Gly	missense_variant	2/7		NM_022101.4	ENSP00000494123.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 107 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Dec 12, 2018

The STEEP1 c.169C>G p.(Arg57Gly) missense variant, to our knowledge, has not been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 or version 4.0.0 of the Genome Aggregation Database. Based on the available evidence, the c.169C>G p.(Arg57Gly) variant is classified as a variant of uncertain significance for X-linked intellectual disability. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	.;.;D
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.3	.;M;M
PROVEAN	Pathogenic	-5.7	D;D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.0060	D;D;.
Polyphen		0.93	.;.;P
Vest4		0.81
MutPred		0.36		.;Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);
MVP		0.86
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.78
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-118694304;