rs10054991

Variant names:

• chr5-137224123-A-G
• rs10054991
• NM_004598.4:c.232+42887T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004598.4(SPOCK1):​c.232+42887T>C variant causes a intron change. The variant allele was found at a frequency of 0.17 in 152,266 control chromosomes in the GnomAD database, including 2,504 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 0.17 (2504 hom., cov: 33)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 5 publications found

Genes affected

SPOCK1 (HGNC:11251): (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1) This gene encodes the protein core of a seminal plasma proteoglycan containing chondroitin- and heparan-sulfate chains. The protein's function is unknown, although similarity to thyropin-type cysteine protease-inhibitors suggests its function may be related to protease inhibition. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK1	NM_004598.4	c.232+42887T>C		intron_variant	Intron 3 of 10	ENST00000394945.6	NP_004589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK1	ENST00000394945.6	c.232+42887T>C		intron_variant	Intron 3 of 10	1	NM_004598.4	ENSP00000378401.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25865 AN: 152148 Hom.: 2500 Cov.: 33

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.182

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.170 AC: 25886 AN: 152266 Hom.: 2504 Cov.: 33 AF XY: 0.171 AC XY: 12734 AN XY: 74440

African (AFR) AF: 0.0962 AC: 3998 AN: 41578

American (AMR) AF: 0.141 AC: 2162 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3468

East Asian (EAS) AF: 0.111 AC: 576 AN: 5172

South Asian (SAS) AF: 0.267 AC: 1288 AN: 4816

European-Finnish (FIN) AF: 0.239 AC: 2538 AN: 10610

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14075 AN: 68008

Other (OTH) AF: 0.187 AC: 395 AN: 2114

Alfa AF: 0.176 Hom.: 512

Bravo AF: 0.157

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Benign	0.82
PhyloP100		3.6
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs10054991; hg19: chr5-136559812;