rs147816230

Variant names:

• chr4-166735014-G-A
• rs147816230
• NM_001040159.2:c.1209C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-166735014-G-A
• chr4-166735014-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001040159.2(SPOCK3):​c.1209C>T​(p.Asp403Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000896 in 1,562,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: SPOCK3 NM_001040159.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

Genes affected

SPOCK3 (HGNC:13565): (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 3) This gene encodes a member of a novel family of calcium-binding proteoglycan proteins that contain thyroglobulin type-1 and Kazal-like domains. The encoded protein and may play a role in adult T-cell leukemia by inhibiting the activity of membrane-type matrix metalloproteinases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=0.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK3	NM_001040159.2	c.1209C>T	p.Asp403Asp	synonymous_variant	Exon 11 of 11	ENST00000357545.9	NP_001035249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK3	ENST00000357545.9	c.1209C>T	p.Asp403Asp	synonymous_variant	Exon 11 of 11	1	NM_001040159.2	ENSP00000350153.4

Frequencies

GnomAD3 genomes AF: 0.000345 AC: 52 AN: 150598 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000162 AC: 40 AN: 246838 Hom.: 0 AF XY: 0.000112 AC XY: 15 AN XY: 133690

Gnomad AFR exome AF: 0.000929

Gnomad AMR exome AF: 0.0000880

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000935

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000363

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000623 AC: 88 AN: 1411562 Hom.: 0 Cov.: 24 AF XY: 0.0000581 AC XY: 41 AN XY: 705170

Gnomad4 AFR exome AF: 0.00123

Gnomad4 AMR exome AF: 0.0000902

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000306

Gnomad4 SAS exome AF: 0.0000472

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000178

Gnomad4 OTH exome AF: 0.000153

GnomAD4 genome AF: 0.000345 AC: 52 AN: 150716 Hom.: 0 Cov.: 32 AF XY: 0.000354 AC XY: 26 AN XY: 73518

Gnomad4 AFR AF: 0.00117

Gnomad4 AMR AF: 0.000133

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000364 Hom.: 0

Bravo AF: 0.000438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.32
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs147816230; hg19: chr4-167656165; COSMIC: COSV62730777;