chr2-230172144-C-T

Variant names:

• chr2-230172144-C-T
• rs3948463
• NM_080424.4:c.1737G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080424.4(SP110):​c.1737G>A​(p.Met579Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 1,611,874 control chromosomes in the GnomAD database, including 4,258 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (301 hom., cov: 33)
  • Exomes 𝑓: 0.069 (3957 hom.)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.229
• Publications: 18 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), Orphanet, ClinGen, Ambry Genetics

ENSG00000225963 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022109747).
• BP6: Variant 2-230172144-C-T is Benign according to our data. Variant chr2-230172144-C-T is described in ClinVar as Benign. ClinVar VariationId is 334897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.1737G>A	p.Met579Ile	missense_variant	Exon 16 of 19	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1737G>A	p.Met579Ile	missense_variant	Exon 16 of 19	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8089 AN: 152208 Hom.: 301 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0538

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0632

GnomAD2 exomes AF: 0.0599 AC: 15056 AN: 251380 AF XY: 0.0620

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.0357

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.00299

Gnomad FIN exome AF: 0.0315

Gnomad NFE exome AF: 0.0818

Gnomad OTH exome AF: 0.0740

GnomAD4 exome AF: 0.0689 AC: 100601 AN: 1459548 Hom.: 3957 Cov.: 30 AF XY: 0.0690 AC XY: 50146 AN XY: 726272

African (AFR) AF: 0.0125 AC: 419 AN: 33448

American (AMR) AF: 0.0383 AC: 1715 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3795 AN: 26120

East Asian (EAS) AF: 0.00159 AC: 63 AN: 39680

South Asian (SAS) AF: 0.0525 AC: 4527 AN: 86222

European-Finnish (FIN) AF: 0.0330 AC: 1763 AN: 53414

Middle Eastern (MID) AF: 0.0866 AC: 499 AN: 5760

European-Non Finnish (NFE) AF: 0.0755 AC: 83770 AN: 1109846

Other (OTH) AF: 0.0671 AC: 4050 AN: 60334

GnomAD4 genome AF: 0.0531 AC: 8082 AN: 152326 Hom.: 301 Cov.: 33 AF XY: 0.0508 AC XY: 3783 AN XY: 74476

African (AFR) AF: 0.0131 AC: 545 AN: 41582

American (AMR) AF: 0.0520 AC: 796 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5182

South Asian (SAS) AF: 0.0528 AC: 255 AN: 4830

European-Finnish (FIN) AF: 0.0339 AC: 360 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5424 AN: 68026

Other (OTH) AF: 0.0625 AC: 132 AN: 2112

Alfa AF: 0.0716 Hom.: 1399

Bravo AF: 0.0522

TwinsUK AF: 0.0709 AC: 263

ALSPAC AF: 0.0721 AC: 278

ESP6500AA AF: 0.0168 AC: 74

ESP6500EA AF: 0.0826 AC: 710

ExAC AF: 0.0606 AC: 7353

Asia WGS AF: 0.0280 AC: 97 AN: 3478

EpiCase AF: 0.0806

EpiControl AF: 0.0835

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.1
DANN	Benign	0.64
DEOGEN2	Benign	0.0048	.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.82	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L;L
PhyloP100		-0.23
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.16
Sift	Benign	0.48	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.046	B;B
Vest4		0.094
MutPred		0.77		Gain of methylation at K580 (P = 0.0439);Gain of methylation at K580 (P = 0.0439);
MPC		0.16
ClinPred		0.00030	T
GERP RS		2.7
Varity_R		0.065
gMVP		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs3948463; hg19: chr2-231036860; COSMIC: COSV51250701; COSMIC: COSV51250701;