chrX-47201619-C-G

Variant names:

• chrX-47201619-C-G
• rs4239964
• NM_003334.4:c.811+9C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_003334.4(UBA1):​c.811+9C>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 0.99 (37872 hom., 32775 hem., cov: 23)
  • Exomes 𝑓: 0.98 (355394 hom. 356236 hem.)
  • Failed GnomAD Quality Control
• Consequence: UBA1 NM_003334.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.363
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-47201619-C-G is Benign according to our data. Variant chrX-47201619-C-G is described in ClinVar as Benign. ClinVar VariationId is 368331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.811+9C>G		intron	N/A	NP_003325.2
	UBA1	NM_001440807.1		c.853+9C>G		intron	N/A	NP_001427736.1
	UBA1	NM_001440809.1		c.829+9C>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.811+9C>G		intron	N/A	ENSP00000338413.6	P22314-1
	UBA1	ENST00000377351.8	TSL:1	c.811+9C>G		intron	N/A	ENSP00000366568.4	P22314-1
	UBA1	ENST00000880189.1		c.946+9C>G		intron	N/A	ENSP00000550248.1

Frequencies

GnomAD3 genomes AF: 0.986 AC: 109502 AN: 111040 Hom.: 37880 Cov.: 23

Gnomad AFR AF: 0.997

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.983

GnomAD2 exomes AF: 0.980 AC: 178301 AN: 182014 AF XY: 0.976

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.981

Gnomad EAS exome AF: 0.953

Gnomad FIN exome AF: 0.995

Gnomad NFE exome AF: 0.984

Gnomad OTH exome AF: 0.978

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.983 AC: 1078778 AN: 1097948 Hom.: 355394 Cov.: 45 AF XY: 0.980 AC XY: 356236 AN XY: 363330

African (AFR) AF: 0.998 AC: 26341 AN: 26400

American (AMR) AF: 0.992 AC: 34924 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 19031 AN: 19383

East Asian (EAS) AF: 0.972 AC: 29365 AN: 30205

South Asian (SAS) AF: 0.934 AC: 50516 AN: 54100

European-Finnish (FIN) AF: 0.994 AC: 40282 AN: 40521

Middle Eastern (MID) AF: 0.974 AC: 3990 AN: 4095

European-Non Finnish (NFE) AF: 0.985 AC: 829235 AN: 841967

Other (OTH) AF: 0.979 AC: 45094 AN: 46083

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.986 AC: 109552 AN: 111094 Hom.: 37872 Cov.: 23 AF XY: 0.986 AC XY: 32775 AN XY: 33256

African (AFR) AF: 0.997 AC: 30387 AN: 30481

American (AMR) AF: 0.990 AC: 10382 AN: 10485

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 2588 AN: 2641

East Asian (EAS) AF: 0.953 AC: 3346 AN: 3510

South Asian (SAS) AF: 0.935 AC: 2418 AN: 2585

European-Finnish (FIN) AF: 0.996 AC: 5918 AN: 5944

Middle Eastern (MID) AF: 0.986 AC: 214 AN: 217

European-Non Finnish (NFE) AF: 0.984 AC: 52203 AN: 53040

Other (OTH) AF: 0.978 AC: 1480 AN: 1513

Alfa AF: 0.980 Hom.: 8268

Bravo AF: 0.987

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Infantile-onset X-linked spinal muscular atrophy (4)
-	-	4	not specified (4)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.7
DANN	Benign	0.50
PhyloP100		0.36
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4239964; hg19: chrX-47061018;