2-230168917-ATTT-ATTTTTTTTTTTTTT

Variant names:

• chr2-230168917-A-ATTTTTTTTTTT
• rs1553839905
• NM_080424.4:c.*196_*206dupAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_080424.4(SP110):​c.*196_*206dupAAAAAAAAAAA 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: 𝑓 0.00023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (3 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.*196_*206dupAAAAAAAAAAA		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.*196_*206dupAAAAAAAAAAA		3_prime_UTR_variant	Exon 19 of 19	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 34 AN: 148106 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000202

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000433

Gnomad OTH AF: 0.000491

GnomAD4 exome AF: 0.00120 AC: 334 AN: 277716 Hom.: 3 Cov.: 0 AF XY: 0.00108 AC XY: 160 AN XY: 148036

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

African (AFR) AF: 0.000228 AC: 2 AN: 8766

American (AMR) AF: 0.000993 AC: 13 AN: 13090

Ashkenazi Jewish (ASJ) AF: 0.000241 AC: 2 AN: 8296

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

South Asian (SAS) AF: 0.000688 AC: 24 AN: 34892

European-Finnish (FIN) AF: 0.000876 AC: 13 AN: 14840

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

European-Non Finnish (NFE) AF: 0.00166 AC: 267 AN: 160530

Other (OTH) AF: 0.000833 AC: 13 AN: 15598

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000230 AC: 34 AN: 148106 Hom.: 0 Cov.: 0 AF XY: 0.000194 AC XY: 14 AN XY: 71984

African (AFR) AF: 0.0000248 AC: 1 AN: 40266

American (AMR) AF: 0.000202 AC: 3 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.00 AC: 0 AN: 4722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000433 AC: 29 AN: 67026

Other (OTH) AF: 0.000491 AC: 1 AN: 2036

Alfa AF: 0.00 Hom.: 25

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;