X-119544401-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_022101.4(STEEP1):c.375C>T(p.Gly125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (13688 hom., 18693 hem., cov: 22)
  • Exomes 𝑓: 0.63 (145135 hom. 228198 hem.)
  • Failed GnomAD Quality Control
• Consequence: STEEP1 NM_022101.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.376

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant X-119544401-G-A is Benign according to our data. Variant chrX-119544401-G-A is described in ClinVar as [Benign]. Clinvar id is 1255437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.376 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 13693 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEEP1	NM_022101.4	c.375C>T	p.Gly125=	synonymous_variant	4/7	ENST00000644802.2
STEEP1	NM_001170570.2	c.333C>T	p.Gly111=	synonymous_variant	3/6
STEEP1	NM_001170569.1	c.228C>T	p.Gly76=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEEP1	ENST00000644802.2	c.375C>T	p.Gly125=	synonymous_variant	4/7		NM_022101.4	P1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 64220 AN: 109431 Hom.: 13693 Cov.: 22 AF XY: 0.588 AC XY: 18659 AN XY: 31743

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.616

GnomAD3 exomes AF: 0.642 AC: 117575 AN: 183160 Hom.: 23968 AF XY: 0.646 AC XY: 43696 AN XY: 67634

Gnomad AFR exome AF: 0.467

Gnomad AMR exome AF: 0.684

Gnomad ASJ exome AF: 0.676

Gnomad EAS exome AF: 0.787

Gnomad SAS exome AF: 0.671

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.626

Gnomad OTH exome AF: 0.632

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.629 AC: 688939 AN: 1095839 Hom.: 145135 Cov.: 30 AF XY: 0.631 AC XY: 228198 AN XY: 361753

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.678

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.621

Gnomad4 NFE exome AF: 0.624

Gnomad4 OTH exome AF: 0.628

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.587 AC: 64240 AN: 109482 Hom.: 13688 Cov.: 22 AF XY: 0.588 AC XY: 18693 AN XY: 31806

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.621

Alfa AF: 0.609 Hom.: 6751

Bravo AF: 0.593

EpiCase AF: 0.633

EpiControl AF: 0.632

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Intellectual disability, X-linked 107 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	4.9
Dann	Benign	0.65

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: rs5910611; hg19: chrX-118678364; COSMIC: COSV57439061; COSMIC: COSV57439061;