Genetic Variant SP110:c.*206delA (chr2-230168917-AT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_080424.4(SP110):c.*206delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.022 ( 70 hom., cov: 0)

Exomes 𝑓: 0.085 ( 67 hom. )

Consequence

SP110
NM_080424.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -1.76

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.*206delA		3_prime_UTR_variant	Exon 19 of 19	ENST00000258381.11	NP_536349.3	Q9HB58-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 link	c.*206delA		3_prime_UTR_variant	Exon 19 of 19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3284

AN:

147992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00634

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.0195

Gnomad EAS

AF:

0.00413

Gnomad SAS

AF:

0.0695

Gnomad FIN

AF:

0.0254

Gnomad MID

AF:

0.0455

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0167

GnomAD4 exome

AF:

0.0845

AC:

23152

AN:

273982

Hom.:

Cov.:

AF XY:

0.0875

AC XY:

12776

AN XY:

146034

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0727

AC:

624

AN:

8580

American (AMR)

AF:

0.0928

AC:

1191

AN:

12828

Ashkenazi Jewish (ASJ)

AF:

0.0662

AC:

543

AN:

8204

East Asian (EAS)

AF:

0.120

AC:

2399

AN:

19926

South Asian (SAS)

AF:

0.123

AC:

4225

AN:

34332

European-Finnish (FIN)

AF:

0.0780

AC:

1142

AN:

14650

Middle Eastern (MID)

AF:

0.0914

AC:

104

AN:

1138

European-Non Finnish (NFE)

AF:

0.0736

AC:

11700

AN:

158892

Other (OTH)

AF:

0.0793

AC:

1224

AN:

15432

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.370

Heterozygous variant carriers

1200

2399

3599

4798

5998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0222

AC:

3284

AN:

148062

Hom.:

Cov.:

AF XY:

0.0220

AC XY:

1584

AN XY:

72000

show subpopulations

African (AFR)

AF:

0.00635

AC:

256

AN:

40340

American (AMR)

AF:

0.00995

AC:

148

AN:

14880

Ashkenazi Jewish (ASJ)

AF:

0.0195

AC:

AN:

3434

East Asian (EAS)

AF:

0.00415

AC:

AN:

5066

South Asian (SAS)

AF:

0.0695

AC:

327

AN:

4708

European-Finnish (FIN)

AF:

0.0254

AC:

239

AN:

9426

Middle Eastern (MID)

AF:

0.0461

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0325

AC:

2177

AN:

66978

Other (OTH)

AF:

0.0171

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

138

276

415

553

691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0294

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hepatic veno-occlusive disease-immunodeficiency syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr2-230168917-AT-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over