2-230168917-ATTT-ATTTT

Variant names:

• chr2-230168917-A-AT
• rs1553839905
• NM_080424.4:c.*206dupA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_080424.4(SP110):​c.*206dupA 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 0.00024 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0095 (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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000236 (35/148172) while in subpopulation EAS AF = 0.00118 (6/5068). AF 95% confidence interval is 0.000515. There are 1 homozygotes in GnomAd4. There are 16 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.*206dupA		3_prime_UTR	Exon 19 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.*206dupA		3_prime_UTR	Exon 20 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.*206dupA		3_prime_UTR	Exon 19 of 19	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.*206dupA		3_prime_UTR	Exon 19 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.*206dupA		3_prime_UTR	Exon 18 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000897327.1		c.*206dupA		splice_region	Exon 19 of 19	ENSP00000567386.1

Frequencies

GnomAD3 genomes AF: 0.000236 AC: 35 AN: 148102 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000605

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000134

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00950 AC: 2631 AN: 276968 Hom.: 0 Cov.: 0 AF XY: 0.00939 AC XY: 1387 AN XY: 147646

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

African (AFR) AF: 0.0124 AC: 108 AN: 8714

American (AMR) AF: 0.0113 AC: 147 AN: 13014

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 74 AN: 8290

East Asian (EAS) AF: 0.0224 AC: 457 AN: 20404

South Asian (SAS) AF: 0.00906 AC: 315 AN: 34760

European-Finnish (FIN) AF: 0.0104 AC: 154 AN: 14798

Middle Eastern (MID) AF: 0.00436 AC: 5 AN: 1148

European-Non Finnish (NFE) AF: 0.00768 AC: 1231 AN: 160268

Other (OTH) AF: 0.00899 AC: 140 AN: 15572

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000236 AC: 35 AN: 148172 Hom.: 1 Cov.: 0 AF XY: 0.000222 AC XY: 16 AN XY: 72062

African (AFR) AF: 0.000248 AC: 10 AN: 40358

American (AMR) AF: 0.000604 AC: 9 AN: 14902

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

East Asian (EAS) AF: 0.00118 AC: 6 AN: 5068

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4712

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000134 AC: 9 AN: 67018

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.00 Hom.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;