Variant 4-87493595-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004684.6(SPARCL1):c.1205G>A(p.Gly402Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,607,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SPARCL1
NM_004684.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.263

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08406106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPARCL1	NM_004684.6 linkuse as main transcript	c.1205G>A	p.Gly402Glu	missense_variant	4/11	ENST00000282470.11	NP_004675.3
SPARCL1	NM_001128310.3 linkuse as main transcript	c.1205G>A	p.Gly402Glu	missense_variant	5/12		NP_001121782.1
SPARCL1	NM_001291976.2 linkuse as main transcript	c.830G>A	p.Gly277Glu	missense_variant	5/12		NP_001278905.1
SPARCL1	NM_001291977.2 linkuse as main transcript	c.830G>A	p.Gly277Glu	missense_variant	3/10		NP_001278906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPARCL1	ENST00000282470.11 linkuse as main transcript	c.1205G>A	p.Gly402Glu	missense_variant	4/11	1	NM_004684.6	ENSP00000282470	P2	Q14515-1
SPARCL1	ENST00000418378.5 linkuse as main transcript	c.1205G>A	p.Gly402Glu	missense_variant	5/12	5		ENSP00000414856	P2	Q14515-1
SPARCL1	ENST00000503414.5 linkuse as main transcript	c.830G>A	p.Gly277Glu	missense_variant	5/12	2		ENSP00000422903	A2	Q14515-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247442

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1455566

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

723404

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.1205G>A (p.G402E) alteration is located in exon 5 (coding exon 3) of the SPARCL1 gene. This alteration results from a G to A substitution at nucleotide position 1205, causing the glycine (G) at amino acid position 402 to be replaced by a glutamic acid (E). 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

0.079

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.85

DANN

Benign

0.93

DEOGEN2

Benign

0.035

T;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.61

.;T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.0

M;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.060

N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.099

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.96

D;D;.

Vest4

0.093

MutPred

0.25

Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);.;

MVP

0.49

MPC

0.12

ClinPred

0.23

GERP RS

-1.1

Varity_R

0.041

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over