NM_003118.4:c.873C>T

Variant names:

• chr5-151664097-G-A
• NM_003118.4:c.873C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_003118.4(SPARC):​c.873C>T​(p.Gly291Gly) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPARC NM_003118.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

SPARC (HGNC:11219): (secreted protein acidic and cysteine rich) This gene encodes a cysteine-rich acidic matrix-associated protein. The encoded protein is required for the collagen in bone to become calcified but is also involved in extracellular matrix synthesis and promotion of changes to cell shape. The gene product has been associated with tumor suppression but has also been correlated with metastasis based on changes to cell shape which can promote tumor cell invasion. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2015]

SPARC Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 17

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae)
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 5-151664097-G-A is Benign according to our data. Variant chr5-151664097-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3054232.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.29 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003118.4. 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
	SPARC	NM_003118.4	MANE Select	c.873C>T	p.Gly291Gly	synonymous	Exon 9 of 10	NP_003109.1	P09486
	SPARC	NM_001309444.2		c.873C>T	p.Gly291Gly	synonymous	Exon 9 of 10	NP_001296373.1
	SPARC	NM_001309443.2		c.870C>T	p.Gly290Gly	synonymous	Exon 9 of 10	NP_001296372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARC	ENST00000231061.9	TSL:1 MANE Select	c.873C>T	p.Gly291Gly	synonymous	Exon 9 of 10	ENSP00000231061.4	P09486
	SPARC	ENST00000896427.1		c.873C>T	p.Gly291Gly	synonymous	Exon 10 of 11	ENSP00000566486.1
	SPARC	ENST00000896428.1		c.873C>T	p.Gly291Gly	synonymous	Exon 9 of 10	ENSP00000566487.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SPARC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr5-151043658;