NM_080862.3:c.694+13573G>A

Variant names:

• chr3-141080371-G-A
• rs16851055
• NM_080862.3:c.694+13573G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080862.3(SPSB4):​c.694+13573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,242 control chromosomes in the GnomAD database, including 6,062 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (6061 hom., cov: 33)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: SPSB4 NM_080862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 14 publications found

Genes affected

SPSB4 (HGNC:30630): (splA/ryanodine receptor domain and SOCS box containing 4) Enables ubiquitin ligase-substrate adaptor activity. Involved in cellular protein metabolic process; positive regulation of protein polyubiquitination; and regulation of circadian rhythm. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080862.3. 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
	SPSB4	NM_080862.3	MANE Select	c.694+13573G>A		intron	N/A	NP_543138.1	Q96A44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB4	ENST00000310546.3	TSL:1 MANE Select	c.694+13573G>A		intron	N/A	ENSP00000311609.2	Q96A44
	SPSB4	ENST00000887577.1		c.694+13573G>A		intron	N/A	ENSP00000557636.1
	SPSB4	ENST00000931037.1		c.694+13573G>A		intron	N/A	ENSP00000601096.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38533 AN: 152102 Hom.: 6055 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.364 AC: 8 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.389 AC XY: 7 AN XY: 18

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.350 AC: 7 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.253 AC: 38568 AN: 152220 Hom.: 6061 Cov.: 33 AF XY: 0.246 AC XY: 18322 AN XY: 74426

African (AFR) AF: 0.438 AC: 18169 AN: 41502

American (AMR) AF: 0.175 AC: 2678 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5180

South Asian (SAS) AF: 0.132 AC: 637 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1154 AN: 10618

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13147 AN: 68008

Other (OTH) AF: 0.240 AC: 506 AN: 2112

Alfa AF: 0.217 Hom.: 12560

Bravo AF: 0.266

Asia WGS AF: 0.185 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.62
PhyloP100		-0.47
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: rs16851055; hg19: chr3-140799213;