2-230169147-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080424.4(SP110):c.2119G>A(p.Gly707Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. G707D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.182

Publications

0 publications found

Variant links:

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

SP110 links:

ENSG00000225963 (HGNC:):

ENSG00000225963 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035893172).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SP110	NM_080424.4	MANE Select	c.2119G>A	p.Gly707Ser	missense	Exon 19 of 19	NP_536349.3	Q9HB58-6
SP110	NM_001378442.1		c.2215G>A	p.Gly739Ser	missense	Exon 20 of 20	NP_001365371.1
SP110	NM_001378443.1		c.2197G>A	p.Gly733Ser	missense	Exon 19 of 19	NP_001365372.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SP110	ENST00000258381.11	TSL:2 MANE Select	c.2119G>A	p.Gly707Ser	missense	Exon 19 of 19	ENSP00000258381.6	Q9HB58-6
SP110	ENST00000358662.9	TSL:1	c.2047G>A	p.Gly683Ser	missense	Exon 18 of 18	ENSP00000351488.4	Q9HB58-1
SP110	ENST00000897327.1		c.2047G>A	p.Gly683Ser	missense	Exon 19 of 19	ENSP00000567386.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460768

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111050

Other (OTH)

AF:

0.00

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.58

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.00072

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.36

M_CAP

Benign

0.0039

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

PhyloP100

0.18

PrimateAI

Benign

0.29

PROVEAN

Benign

1.1

REVEL

Benign

0.017

Sift

Benign

0.75

Sift4G

Benign

0.60

Polyphen

0.0020

Vest4

0.098

MutPred

0.23

Gain of glycosylation at G683 (P = 0.0043)

MVP

0.17

MPC

0.56

ClinPred

0.042

GERP RS

-1.5

Varity_R

0.015

gMVP

0.16

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over