X-47198248-A-G

Variant names:

• chrX-47198248-A-G
• rs4468050
• NM_003334.4:c.1-555A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_003334.4(UBA1):​c.1-555A>G variant causes a intron 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 1.0 (38822 hom., 31759 hem., cov: 22)
  • Exomes 𝑓: 1.0 (293335 hom. 282199 hem.)
  • Failed GnomAD Quality Control
• Consequence: UBA1 NM_003334.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.641
• Publications: 7 publications found

Genes affected

UBA1 (HGNC:12469): (ubiquitin like modifier activating enzyme 1) The protein encoded by this gene catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation. This gene complements an X-linked mouse temperature-sensitive defect in DNA synthesis, and thus may function in DNA repair. It is part of a gene cluster on chromosome Xp11.23. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

UBA1 Gene-Disease associations (from GenCC):

• infantile-onset X-linked spinal muscular atrophy

  Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• inflammatory disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2715918E-6).
• BP6: Variant X-47198248-A-G is Benign according to our data. Variant chrX-47198248-A-G is described in ClinVar as Benign. ClinVar VariationId is 2688098.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003334.4. 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
	UBA1	NM_003334.4	MANE Select	c.1-555A>G		intron	N/A	NP_003325.2
	UBA1	NM_001440807.1		c.-5-61A>G		intron	N/A	NP_001427736.1
	UBA1	NM_001440809.1		c.19-555A>G		intron	N/A	NP_001427738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA1	ENST00000335972.11	TSL:1 MANE Select	c.1-555A>G		intron	N/A	ENSP00000338413.6	P22314-1
	UBA1	ENST00000377351.8	TSL:1	c.1-555A>G		intron	N/A	ENSP00000366568.4	P22314-1
	UBA1	ENST00000451702.2	TSL:5	c.46A>G	p.Ile16Val	missense	Exon 1 of 6	ENSP00000401101.1	Q5JRS2

Frequencies

GnomAD3 genomes AF: 0.999 AC: 109431 AN: 109546 Hom.: 38827 Cov.: 22

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.999

GnomAD2 exomes AF: 0.998 AC: 108363 AN: 108573 AF XY: 0.998

Gnomad AFR exome AF: 0.999

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.975

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 869089 AN: 869411 Hom.: 293335 Cov.: 42 AF XY: 1.00 AC XY: 282199 AN XY: 282297

African (AFR) AF: 1.00 AC: 19297 AN: 19305

American (AMR) AF: 1.00 AC: 22247 AN: 22247

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 11947 AN: 11947

East Asian (EAS) AF: 0.975 AC: 9468 AN: 9708

South Asian (SAS) AF: 1.00 AC: 47665 AN: 47688

European-Finnish (FIN) AF: 1.00 AC: 20866 AN: 20866

Middle Eastern (MID) AF: 1.00 AC: 3150 AN: 3150

European-Non Finnish (NFE) AF: 1.00 AC: 702691 AN: 702698

Other (OTH) AF: 0.999 AC: 31758 AN: 31802

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.999 AC: 109483 AN: 109598 Hom.: 38822 Cov.: 22 AF XY: 0.999 AC XY: 31759 AN XY: 31794

African (AFR) AF: 0.999 AC: 29967 AN: 29990

American (AMR) AF: 1.00 AC: 10249 AN: 10250

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2627 AN: 2627

East Asian (EAS) AF: 0.975 AC: 3389 AN: 3476

South Asian (SAS) AF: 0.999 AC: 2524 AN: 2526

European-Finnish (FIN) AF: 1.00 AC: 5681 AN: 5681

Middle Eastern (MID) AF: 1.00 AC: 214 AN: 214

European-Non Finnish (NFE) AF: 1.00 AC: 52659 AN: 52659

Other (OTH) AF: 0.999 AC: 1496 AN: 1498

Alfa AF: 0.999 Hom.: 16097

Bravo AF: 0.999

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 1.00 AC: 2889

ExAC AF: 0.999 AC: 18883

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.086
DANN	Benign	0.20
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.64
PROVEAN	Benign	0.010	N
REVEL	Benign	0.084
Sift	Pathogenic	0.0	D
ClinPred		0.0023	T
GERP RS		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs4468050; hg19: chrX-47057647; COSMIC: COSV100256269; COSMIC: COSV100256269;