2-230168917-AT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_080424.4(SP110):c.*206del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.022 (70 hom., cov: 0)
  • Exomes 𝑓: 0.085 (67 hom.)
• Consequence: SP110 NM_080424.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.76

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4	c.*206del		3_prime_UTR_variant	19/19	ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11	c.*206del		3_prime_UTR_variant	19/19	2	NM_080424.4	P1
	ENST00000628587.2	n.1003+1279del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3284 AN: 147992 Hom.: 70 Cov.: 0

Gnomad AFR AF: 0.00634

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0195

Gnomad EAS AF: 0.00413

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0455

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.0845 AC: 23152 AN: 273982 Hom.: 67 Cov.: 0 AF XY: 0.0875 AC XY: 12776 AN XY: 146034

Gnomad4 AFR exome AF: 0.0727

Gnomad4 AMR exome AF: 0.0928

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0780

Gnomad4 NFE exome AF: 0.0736

Gnomad4 OTH exome AF: 0.0793

GnomAD4 genome AF: 0.0222 AC: 3284 AN: 148062 Hom.: 70 Cov.: 0 AF XY: 0.0220 AC XY: 1584 AN XY: 72000

Gnomad4 AFR AF: 0.00635

Gnomad4 AMR AF: 0.00995

Gnomad4 ASJ AF: 0.0195

Gnomad4 EAS AF: 0.00415

Gnomad4 SAS AF: 0.0695

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0171

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553839905; hg19: chr2-231033633;