rs181058279

Variant names:

• chr2-230169144-C-G
• rs181058279
• NM_080424.4:c.2122G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-230169144-C-G
• chr2-230169144-C-T
• chr2-230169144-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_080424.4(SP110):​c.2122G>C​(p.Gly708Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000892 in 1,612,512 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). 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: 𝑓 0.00049 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00093 (3 hom.)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: -0.471
• Publications: 7 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), PanelApp Australia, Orphanet, ClinGen, Ambry Genetics

ENSG00000225963 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013007194).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000493 (75/152074) while in subpopulation NFE AF = 0.000839 (57/67976). AF 95% confidence interval is 0.000664. There are 0 homozygotes in GnomAd4. There are 30 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.2122G>C	p.Gly708Arg	missense	Exon 19 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.2218G>C	p.Gly740Arg	missense	Exon 20 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.2200G>C	p.Gly734Arg	missense	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.2122G>C	p.Gly708Arg	missense	Exon 19 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.2050G>C	p.Gly684Arg	missense	Exon 18 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000897327.1		c.2050G>C	p.Gly684Arg	missense	Exon 19 of 19	ENSP00000567386.1

Frequencies

GnomAD3 genomes AF: 0.000494 AC: 75 AN: 151956 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

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: 0.000838

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000378 AC: 95 AN: 251420 AF XY: 0.000390

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000554

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000933 AC: 1363 AN: 1460438 Hom.: 3 Cov.: 29 AF XY: 0.000877 AC XY: 637 AN XY: 726616

African (AFR) AF: 0.000149 AC: 5 AN: 33458

American (AMR) AF: 0.000693 AC: 31 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00117 AC: 1297 AN: 1110716

Other (OTH) AF: 0.000497 AC: 30 AN: 60342

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152074 Hom.: 0 Cov.: 31 AF XY: 0.000404 AC XY: 30 AN XY: 74344

African (AFR) AF: 0.000217 AC: 9 AN: 41482

American (AMR) AF: 0.000524 AC: 8 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000839 AC: 57 AN: 67976

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000721 Hom.: 0

Bravo AF: 0.000487

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.000264 AC: 32

EpiCase AF: 0.000491

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	3	-	Hepatic veno-occlusive disease-immunodeficiency syndrome (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.75
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.47
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.045
Sift	Benign	0.082	T
Sift4G	Benign	0.094	T
Polyphen		0.013	B
Vest4		0.16
MVP		0.23
MPC		0.65
ClinPred		0.027	T
GERP RS		-5.2
Varity_R		0.047
gMVP		0.17
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs181058279; hg19: chr2-231033860; COSMIC: COSV51275354;