chr5-137040361-C-T

Variant names:

• chr5-137040361-C-T
• rs17170899
• NM_004598.4:c.589+27354G>A

Variant summary

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

The NM_004598.4(SPOCK1):​c.589+27354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 152,290 control chromosomes in the GnomAD database, including 160 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 0.043 (160 hom., cov: 33)
• Consequence: SPOCK1 NM_004598.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK1	NM_004598.4	c.589+27354G>A		intron_variant	Intron 6 of 10	ENST00000394945.6	NP_004589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK1	ENST00000394945.6	c.589+27354G>A		intron_variant	Intron 6 of 10	1	NM_004598.4	ENSP00000378401.1
SPOCK1	ENST00000510689.5	c.154+27354G>A		intron_variant	Intron 5 of 5	4		ENSP00000421677.1
SPOCK1	ENST00000635347.1	n.562+27354G>A		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6563 AN: 152172 Hom.: 162 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0430

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0431 AC: 6566 AN: 152290 Hom.: 160 Cov.: 33 AF XY: 0.0419 AC XY: 3123 AN XY: 74470

African (AFR) AF: 0.0429 AC: 1781 AN: 41554

American (AMR) AF: 0.0580 AC: 888 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.0448 AC: 232 AN: 5178

South Asian (SAS) AF: 0.0435 AC: 210 AN: 4826

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0430 AC: 2922 AN: 68018

Other (OTH) AF: 0.0426 AC: 90 AN: 2112

Alfa AF: 0.0434 Hom.: 281

Bravo AF: 0.0469

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.41
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: rs17170899; hg19: chr5-136376050;