chr4-87490860-T-C

Variant names:

• chr4-87490860-T-C
• rs1724298445
• NM_004684.6:c.1310A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004684.6(SPARCL1):​c.1310A>G​(p.Gln437Arg) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPARCL1 NM_004684.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• Publications: 0 publications found

Genes affected

SPARCL1 (HGNC:11220): (SPARC like 1) Predicted to enable calcium ion binding activity; collagen binding activity; and extracellular matrix binding activity. Predicted to be involved in anatomical structure development and regulation of synapse organization. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SPARCL1 Gene-Disease associations (from GenCC):

• corneal dystrophy

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• stromal corneal dystrophy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29979908).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004684.6. 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
	SPARCL1	NM_004684.6	MANE Select	c.1310A>G	p.Gln437Arg	missense	Exon 6 of 11	NP_004675.3
	SPARCL1	NM_001128310.3		c.1310A>G	p.Gln437Arg	missense	Exon 7 of 12	NP_001121782.1	Q14515-1
	SPARCL1	NM_001291976.2		c.935A>G	p.Gln312Arg	missense	Exon 7 of 12	NP_001278905.1	Q14515-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPARCL1	ENST00000282470.11	TSL:1 MANE Select	c.1310A>G	p.Gln437Arg	missense	Exon 6 of 11	ENSP00000282470.6	Q14515-1
	SPARCL1	ENST00000946054.1		c.1310A>G	p.Gln437Arg	missense	Exon 6 of 11	ENSP00000616113.1
	SPARCL1	ENST00000880794.1		c.1310A>G	p.Gln437Arg	missense	Exon 6 of 11	ENSP00000550853.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Benign	0.060
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.031
Sift	Benign	0.081	T
Sift4G	Benign	1.0	T
Polyphen		0.52	P
Vest4		0.20
MutPred		0.31		Gain of MoRF binding (P = 0.019)
MVP		0.30
MPC		0.16
ClinPred		0.75	D
GERP RS		4.9
Varity_R		0.19
gMVP		0.23
Mutation Taster		=93/7	polymorphism

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: rs1724298445; hg19: chr4-88412012;