rs959506

Variant names:

• chr2-230178104-C-A
• rs959506
• NM_080424.4:c.1447+53G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080424.4(SP110):​c.1447+53G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 0 publications found

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]

SP110 Gene-Disease associations (from GenCC):

• hepatic veno-occlusive disease-immunodeficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

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=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.1447+53G>T		intron_variant	Intron 13 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1447+53G>T		intron_variant	Intron 13 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 944654 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 489112

African (AFR) AF: 0.00 AC: 0 AN: 23108

American (AMR) AF: 0.00 AC: 0 AN: 40268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22860

East Asian (EAS) AF: 0.00 AC: 0 AN: 36052

South Asian (SAS) AF: 0.00 AC: 0 AN: 73160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4814

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 649450

Other (OTH) AF: 0.00 AC: 0 AN: 43132

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.73
PhyloP100		0.37

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: rs959506; hg19: chr2-231042820;