3-141080371-G-C

Position:

• chr3-141080371-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080862.3(SPSB4):​c.694+13573G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: SPSB4 NM_080862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPSB4	NM_080862.3	c.694+13573G>C		intron_variant		ENST00000310546.3	NP_543138.1
SPSB4	XM_017007509.3	c.*74G>C		3_prime_UTR_variant	3/3		XP_016862998.1
SPSB4	XR_924215.4	n.1575G>C		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPSB4	ENST00000310546.3	c.694+13573G>C		intron_variant		1	NM_080862.3	ENSP00000311609	P1
SPSB4	ENST00000508126.1	c.161+13573G>C		intron_variant		2		ENSP00000422034
SPSB4	ENST00000507895.1	n.220G>C		non_coding_transcript_exon_variant	2/3	5
SPSB4	ENST00000508828.1	n.535G>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs16851055; hg19: chr3-140799213;