4-87482465-A-T

Position:

• chr4-87482465-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004684.6(SPARCL1):​c.1627T>A​(p.Ser543Thr) 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. 15/21 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: 0.320

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117857724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPARCL1	NM_004684.6	c.1627T>A	p.Ser543Thr	missense_variant	8/11	ENST00000282470.11	NP_004675.3
SPARCL1	NM_001128310.3	c.1627T>A	p.Ser543Thr	missense_variant	9/12		NP_001121782.1
SPARCL1	NM_001291976.2	c.1252T>A	p.Ser418Thr	missense_variant	9/12		NP_001278905.1
SPARCL1	NM_001291977.2	c.1252T>A	p.Ser418Thr	missense_variant	7/10		NP_001278906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000282470.11	c.1627T>A	p.Ser543Thr	missense_variant	8/11	1	NM_004684.6	ENSP00000282470	P2
SPARCL1	ENST00000418378.5	c.1627T>A	p.Ser543Thr	missense_variant	9/12	5		ENSP00000414856	P2
SPARCL1	ENST00000503414.5	c.1252T>A	p.Ser418Thr	missense_variant	9/12	2		ENSP00000422903	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.1627T>A (p.S543T) alteration is located in exon 9 (coding exon 7) of the SPARCL1 gene. This alteration results from a T to A substitution at nucleotide position 1627, causing the serine (S) at amino acid position 543 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.51	.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;.
MutationTaster	Benign	0.88	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.99	N;N;N
REVEL	Benign	0.067
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.50	T;T;T
Polyphen		0.67	P;P;.
Vest4		0.12
MutPred		0.51		Loss of disorder (P = 0.0649);Loss of disorder (P = 0.0649);.;
MVP		0.067
MPC		0.10
ClinPred		0.32	T
GERP RS		3.7
Varity_R		0.088
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-88403617;