chrX-47202951-C-T

Variant names:

• chrX-47202951-C-T
• rs369843264
• NM_003334.4:c.1242C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003334.4(UBA1):​c.1242C>T​(p.Ser414Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,209,369 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 136 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 0.00032 (0 hom., 10 hem., cov: 23)
  • Exomes 𝑓: 0.00034 (0 hom. 126 hem.)
• Consequence: UBA1 NM_003334.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.49
• Publications: 2 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant X-47202951-C-T is Benign according to our data. Variant chrX-47202951-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 368334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.49 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 10 XL,Unknown gene

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.1242C>T	p.Ser414Ser	synonymous	Exon 12 of 26	NP_003325.2
	UBA1	NM_001440807.1		c.1284C>T	p.Ser428Ser	synonymous	Exon 13 of 27	NP_001427736.1
	UBA1	NM_001440809.1		c.1260C>T	p.Ser420Ser	synonymous	Exon 13 of 27	NP_001427738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA1	ENST00000335972.11	TSL:1 MANE Select	c.1242C>T	p.Ser414Ser	synonymous	Exon 12 of 26	ENSP00000338413.6	P22314-1
	UBA1	ENST00000377351.8	TSL:1	c.1242C>T	p.Ser414Ser	synonymous	Exon 12 of 26	ENSP00000366568.4	P22314-1
	UBA1	ENST00000880189.1		c.1377C>T	p.Ser459Ser	synonymous	Exon 13 of 27	ENSP00000550248.1

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 36 AN: 111686 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000189

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000285

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000565

Gnomad OTH AF: 0.000666

GnomAD2 exomes AF: 0.000300 AC: 55 AN: 183147 AF XY: 0.000355

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000251

Gnomad NFE exome AF: 0.000587

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000337 AC: 370 AN: 1097683 Hom.: 0 Cov.: 32 AF XY: 0.000347 AC XY: 126 AN XY: 363051

African (AFR) AF: 0.0000379 AC: 1 AN: 26395

American (AMR) AF: 0.000142 AC: 5 AN: 35201

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54111

European-Finnish (FIN) AF: 0.000247 AC: 10 AN: 40526

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4135

European-Non Finnish (NFE) AF: 0.000410 AC: 345 AN: 841655

Other (OTH) AF: 0.000174 AC: 8 AN: 46073

GnomAD4 genome AF: 0.000322 AC: 36 AN: 111686 Hom.: 0 Cov.: 23 AF XY: 0.000295 AC XY: 10 AN XY: 33872

African (AFR) AF: 0.0000652 AC: 2 AN: 30657

American (AMR) AF: 0.000189 AC: 2 AN: 10591

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.000285 AC: 1 AN: 3514

South Asian (SAS) AF: 0.00 AC: 0 AN: 2695

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6069

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000565 AC: 30 AN: 53089

Other (OTH) AF: 0.000666 AC: 1 AN: 1501

Alfa AF: 0.000391 Hom.: 3

Bravo AF: 0.000287

EpiCase AF: 0.00104

EpiControl AF: 0.000653

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Infantile-onset X-linked spinal muscular atrophy (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	UBA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=99/1	polymorphism

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: rs369843264; hg19: chrX-47062350;