X-47198874-C-T

Variant names:

• chrX-47198874-C-T
• rs1329218682
• NM_003334.4:c.72C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_003334.4(UBA1):​c.72C>T​(p.Ser24Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000364 in 1,098,256 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000036 (0 hom. 1 hem.)
• Consequence: UBA1 NM_003334.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant X-47198874-C-T is Benign according to our data. Variant chrX-47198874-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1939806.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA1	NM_003334.4	c.72C>T	p.Ser24Ser	synonymous_variant	Exon 2 of 26	ENST00000335972.11	NP_003325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA1	ENST00000335972.11	c.72C>T	p.Ser24Ser	synonymous_variant	Exon 2 of 26	1	NM_003334.4	ENSP00000338413.6

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1098256 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363610

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 26403

Gnomad4 AMR exome AF: 0.0000284 AC: 1 AN: 35206

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 19386

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 30206

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 54149

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 40534

Gnomad4 NFE exome AF: 0.00000356 AC: 3 AN: 842138

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 46097

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Infantile-onset X-linked spinal muscular atrophy Benign:1

Jul 19, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.8
DANN	Benign	0.80
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

Other links and lift over

dbSNP: rs1329218682; hg19: chrX-47058273;