chr2-230177560-A-G

Variant names:

• chr2-230177560-A-G
• rs1135791
• NM_080424.4:c.1568T>C

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.1568T>C​(p.Met523Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,612,900 control chromosomes in the GnomAD database, including 183,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13277 hom., cov: 32)
  • Exomes 𝑓: 0.48 (170437 hom.)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.542
• Publications: 50 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.4625439E-5).
• BP6: Variant 2-230177560-A-G is Benign according to our data. Variant chr2-230177560-A-G is described in ClinVar as Benign. ClinVar VariationId is 334902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

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.1568T>C	p.Met523Thr	missense	Exon 14 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.1586T>C	p.Met529Thr	missense	Exon 15 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.1568T>C	p.Met523Thr	missense	Exon 14 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.1568T>C	p.Met523Thr	missense	Exon 14 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.1568T>C	p.Met523Thr	missense	Exon 14 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.1568T>C	p.Met523Thr	missense	Exon 14 of 15	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60683 AN: 151992 Hom.: 13273 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.417

GnomAD2 exomes AF: 0.419 AC: 105350 AN: 251440 AF XY: 0.430

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.292

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.154

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.476 AC: 695138 AN: 1460788 Hom.: 170437 Cov.: 39 AF XY: 0.476 AC XY: 345962 AN XY: 726768

African (AFR) AF: 0.235 AC: 7867 AN: 33470

American (AMR) AF: 0.302 AC: 13506 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 13528 AN: 26130

East Asian (EAS) AF: 0.169 AC: 6701 AN: 39668

South Asian (SAS) AF: 0.420 AC: 36262 AN: 86244

European-Finnish (FIN) AF: 0.411 AC: 21941 AN: 53410

Middle Eastern (MID) AF: 0.500 AC: 2886 AN: 5768

European-Non Finnish (NFE) AF: 0.509 AC: 565036 AN: 1111012

Other (OTH) AF: 0.454 AC: 27411 AN: 60366

GnomAD4 genome AF: 0.399 AC: 60710 AN: 152112 Hom.: 13277 Cov.: 32 AF XY: 0.392 AC XY: 29179 AN XY: 74356

African (AFR) AF: 0.243 AC: 10087 AN: 41522

American (AMR) AF: 0.373 AC: 5709 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3468

East Asian (EAS) AF: 0.170 AC: 876 AN: 5160

South Asian (SAS) AF: 0.420 AC: 2028 AN: 4824

European-Finnish (FIN) AF: 0.402 AC: 4248 AN: 10572

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.506 AC: 34425 AN: 67968

Other (OTH) AF: 0.419 AC: 884 AN: 2112

Alfa AF: 0.471 Hom.: 39227

Bravo AF: 0.389

TwinsUK AF: 0.513 AC: 1903

ALSPAC AF: 0.499 AC: 1924

ESP6500AA AF: 0.255 AC: 1124

ESP6500EA AF: 0.501 AC: 4306

ExAC AF: 0.426 AC: 51677

Asia WGS AF: 0.279 AC: 973 AN: 3478

EpiCase AF: 0.510

EpiControl AF: 0.516

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hepatic veno-occlusive disease-immunodeficiency syndrome (3)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.36
DANN	Benign	0.28
DEOGEN2	Benign	0.086	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.0044	T
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.85	N
PhyloP100		-0.54
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.15
Sift	Benign	0.28	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.040
MPC		0.15
ClinPred		0.017	T
GERP RS		-0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.033
gMVP		0.51
Mutation Taster		=99/1	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: rs1135791; hg19: chr2-231042276; COSMIC: COSV51247578; COSMIC: COSV51247578;