2-230168917-ATTT-ATTTTTTTTTTT

Variant names:

• chr2-230168917-A-ATTTTTTTT
• rs1553839905
• NM_080424.4:c.*199_*206dupAAAAAAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_080424.4(SP110):​c.*199_*206dupAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0087 (49 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00244 (362/148144) while in subpopulation NFE AF = 0.00363 (243/67010). AF 95% confidence interval is 0.00325. There are 2 homozygotes in GnomAd4. There are 166 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.*199_*206dupAAAAAAAA		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.*199_*206dupAAAAAAAA		3_prime_UTR_variant	Exon 19 of 19	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 363 AN: 148074 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.000874

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00201

Gnomad MID AF: 0.0195

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.00147

GnomAD4 exome AF: 0.00868 AC: 2404 AN: 276896 Hom.: 49 Cov.: 0 AF XY: 0.00858 AC XY: 1267 AN XY: 147584

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

African (AFR) AF: 0.00377 AC: 33 AN: 8750

American (AMR) AF: 0.0102 AC: 133 AN: 13046

Ashkenazi Jewish (ASJ) AF: 0.00845 AC: 70 AN: 8280

East Asian (EAS) AF: 0.0000973 AC: 2 AN: 20556

South Asian (SAS) AF: 0.00862 AC: 300 AN: 34792

European-Finnish (FIN) AF: 0.00723 AC: 107 AN: 14802

Middle Eastern (MID) AF: 0.0140 AC: 16 AN: 1146

European-Non Finnish (NFE) AF: 0.0102 AC: 1633 AN: 159972

Other (OTH) AF: 0.00707 AC: 110 AN: 15552

⚠️ 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: 0.00244 AC: 362 AN: 148144 Hom.: 2 Cov.: 0 AF XY: 0.00230 AC XY: 166 AN XY: 72046

African (AFR) AF: 0.00136 AC: 55 AN: 40354

American (AMR) AF: 0.00221 AC: 33 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.000874 AC: 3 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4712

European-Finnish (FIN) AF: 0.00201 AC: 19 AN: 9432

Middle Eastern (MID) AF: 0.0213 AC: 6 AN: 282

European-Non Finnish (NFE) AF: 0.00363 AC: 243 AN: 67010

Other (OTH) AF: 0.00146 AC: 3 AN: 2052

Alfa AF: 0.00103 Hom.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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;