rs1129411

chr2-230213010-A-Cchr2-230213010-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080424.4(SP110):c.334T>G(p.Trp112Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W112R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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]

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05444339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4	c.334T>G	p.Trp112Gly	missense_variant	4/19	ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11	c.334T>G	p.Trp112Gly	missense_variant	4/19	2	NM_080424.4	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	1.7
Dann	Benign	0.48
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.10	T;T;T;T;T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.054	T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.97	N;N;.;N;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.9	N;N;N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.36	T;T;T;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T;.;T
Polyphen		0.0	B;B;B;.;.;.;.
Vest4		0.15
MutPred		0.63		Gain of disorder (P = 0.0036);Gain of disorder (P = 0.0036);Gain of disorder (P = 0.0036);Gain of disorder (P = 0.0036);.;Gain of disorder (P = 0.0036);.;
MVP		0.13
MPC		0.25
ClinPred		0.063	T
GERP RS		-0.86
Varity_R		0.041
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1129411; hg19: chr2-231077725;