2-230168917-ATTT-ATTTTTTTTTTTTTTTT

Variant names:

• chr2-230168917-A-ATTTTTTTTTTTTT
• rs1553839905
• NM_080424.4:c.*194_*206dupAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_080424.4(SP110):​c.*194_*206dupAAAAAAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: SP110 NM_080424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• 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

ENSG00000225963 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.*194_*206dupAAAAAAAAAAAAA		3_prime_UTR_variant	Exon 19 of 19	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.*194_*206dupAAAAAAAAAAAAA		3_prime_UTR_variant	Exon 19 of 19	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000360 AC: 10 AN: 277836 Hom.: 0 Cov.: 0 AF XY: 0.0000270 AC XY: 4 AN XY: 148104

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 8768

American (AMR) AF: 0.0000764 AC: 1 AN: 13094

Ashkenazi Jewish (ASJ) AF: 0.000120 AC: 1 AN: 8300

East Asian (EAS) AF: 0.00 AC: 0 AN: 20556

South Asian (SAS) AF: 0.00 AC: 0 AN: 34904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1148

European-Non Finnish (NFE) AF: 0.0000436 AC: 7 AN: 160620

Other (OTH) AF: 0.0000641 AC: 1 AN: 15602

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000019), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs1553839905; hg19: chr2-231033633;