2-230177573-G-T

Position:

• chr2-230177573-G-T

Variant summary

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

The NM_080424.4(SP110):​c.1555C>A​(p.Arg519Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,126 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• 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>A	p.Arg519Ser	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>A	p.Arg519Ser	missense_variant	14/19	2	NM_080424.4	ENSP00000258381	P1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74302

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	0.53
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.59	.;D;D;.;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.83	T;T;T;T;T
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.59	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	-4.4	D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.012	D;D;T;T;T
Sift4G	Uncertain	0.016	D;D;T;T;T
Polyphen		0.89	P;D;P;.;.
Vest4		0.21
MutPred		0.67		Loss of MoRF binding (P = 0.0262);Loss of MoRF binding (P = 0.0262);.;Loss of MoRF binding (P = 0.0262);.;
MVP		0.79
MPC		0.38
ClinPred		0.92	D
GERP RS		0.67
Varity_R		0.29
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;