Genetic Variant NM_080424.4:c.*198_*206dupAAAAAAAAA (chr2-230168917-A-ATTTTTTTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_080424.4(SP110):c.*198_*206dupAAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.042 ( 193 hom., cov: 0)

Exomes 𝑓: 0.011 ( 63 hom. )

Failed GnomAD Quality Control

Consequence

SP110
NM_080424.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.198_206dupAAAAAAAAA		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.198_206dupAAAAAAAAA		3_prime_UTR_variant	Exon 19 of 19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6144

AN:

147826

Hom.:

193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.0857

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.00118

Gnomad SAS

AF:

0.0443

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0909

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.0577

GnomAD4 exome

AF:

0.0111

AC:

3074

AN:

276862

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

1634

AN XY:

147570

show subpopulations

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

African (AFR)

AF:

0.00229

AC:

AN:

8752

American (AMR)

AF:

0.0116

AC:

151

AN:

13018

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

8254

East Asian (EAS)

AF:

0.0000486

AC:

AN:

20556

South Asian (SAS)

AF:

0.0112

AC:

391

AN:

34798

European-Finnish (FIN)

AF:

0.00953

AC:

141

AN:

14798

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

1148

European-Non Finnish (NFE)

AF:

0.0132

AC:

2110

AN:

159976

Other (OTH)

AF:

0.0103

AC:

161

AN:

15562

⚠️ 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: 0.381

Heterozygous variant carriers

136

272

409

545

681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0415

AC:

6144

AN:

147896

Hom.:

193

Cov.:

AF XY:

0.0405

AC XY:

2909

AN XY:

71900

show subpopulations

African (AFR)

AF:

0.0164

AC:

661

AN:

40322

American (AMR)

AF:

0.0623

AC:

924

AN:

14836

Ashkenazi Jewish (ASJ)

AF:

0.0755

AC:

259

AN:

3432

East Asian (EAS)

AF:

0.00118

AC:

AN:

5068

South Asian (SAS)

AF:

0.0449

AC:

211

AN:

4704

European-Finnish (FIN)

AF:

0.0188

AC:

177

AN:

9412

Middle Eastern (MID)

AF:

0.0887

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0551

AC:

3687

AN:

66898

Other (OTH)

AF:

0.0572

AC:

117

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

252

504

757

1009

1261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0136

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.8

Splicing

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

Publications

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NM_080424.4:c.198_206dupAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over