2-230169142-ACC-CCT

Variant names:

• chr2-230169142-ACC-CCT
• NM_080424.4:c.2122_2124delGGTinsAGG
• SP110 p.Gly708Arg

Variant summary

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

The NM_080424.4(SP110):​c.2122_2124delGGTinsAGG​(p.Gly708Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G708S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• 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: ClinGen, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000225963 (HGNC:):

ACMG classification

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

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.2122_2124delGGTinsAGG	p.Gly708Arg	missense	N/A	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.2218_2220delGGTinsAGG	p.Gly740Arg	missense	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.2200_2202delGGTinsAGG	p.Gly734Arg	missense	N/A	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.2122_2124delGGTinsAGG	p.Gly708Arg	missense	N/A	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.2050_2052delGGTinsAGG	p.Gly684Arg	missense	N/A	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000897327.1		c.2050_2052delGGTinsAGG	p.Gly684Arg	missense	N/A	ENSP00000567386.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.067

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-231033858;