X-119539766-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_022101.4(STEEP1):​c.630G>A​(p.Ala210Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000572 in 1,205,943 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000058 ( 0 hom. 23 hem. )

Consequence

STEEP1
NM_022101.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
Variant X-119539766-C-T is Benign according to our data. Variant chrX-119539766-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3257093.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 23 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STEEP1NM_022101.4 linkc.630G>A p.Ala210Ala synonymous_variant Exon 7 of 7 ENST00000644802.2 NP_071384.1 Q9H5V9-1
STEEP1NM_001170570.2 linkc.588G>A p.Ala196Ala synonymous_variant Exon 6 of 6 NP_001164041.1 Q9H5V9-3
STEEP1NM_001170569.1 linkc.483G>A p.Ala161Ala synonymous_variant Exon 7 of 7 NP_001164040.1 Q9H5V9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STEEP1ENST00000644802.2 linkc.630G>A p.Ala210Ala synonymous_variant Exon 7 of 7 NM_022101.4 ENSP00000494123.2 Q9H5V9-1

Frequencies

GnomAD3 genomes
AF:
0.0000542
AC:
6
AN:
110781
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
32975
show subpopulations
Gnomad AFR
AF:
0.0000329
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000944
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000219
AC:
4
AN:
182647
Hom.:
0
AF XY:
0.0000149
AC XY:
1
AN XY:
67173
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000528
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000368
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000575
AC:
63
AN:
1095162
Hom.:
0
Cov.:
27
AF XY:
0.0000638
AC XY:
23
AN XY:
360594
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.0000494
Gnomad4 NFE exome
AF:
0.0000679
Gnomad4 OTH exome
AF:
0.0000435
GnomAD4 genome
AF:
0.0000542
AC:
6
AN:
110781
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
32975
show subpopulations
Gnomad4 AFR
AF:
0.0000329
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000944
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
1
Bravo
AF:
0.0000529

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

STEEP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
CADD
Benign
0.50
DANN
Benign
0.72
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745788287; hg19: chrX-118673729; API