2-230177573-G-C

Position:

• chr2-230177573-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080424.4(SP110):​c.1555C>G​(p.Arg519Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_080424.4	c.1555C>G	p.Arg519Gly	missense_variant	14/19	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1555C>G	p.Arg519Gly	missense_variant	14/19	2	NM_080424.4	ENSP00000258381	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251470 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461686 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	1.3
DANN	Benign	0.96
DEOGEN2	Uncertain	0.61	.;D;D;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.84	T;T;T;T;T
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.2	M;M;.;M;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.20	T
PROVEAN	Pathogenic	-5.5	D;D;D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.010	D;D;T;T;T
Sift4G	Uncertain	0.014	D;D;T;T;T
Polyphen		0.89	P;D;P;.;.
Vest4		0.34
MutPred		0.73		Loss of MoRF binding (P = 0.0162);Loss of MoRF binding (P = 0.0162);.;Loss of MoRF binding (P = 0.0162);.;
MVP		0.82
MPC		0.35
ClinPred		0.66	D
GERP RS		0.67
Varity_R		0.30
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs765616523; hg19: chr2-231042289;