Variant 4-87494108-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004684.6(SPARCL1):c.692G>A(p.Ser231Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPARCL1
NM_004684.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00500

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05830428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPARCL1	NM_004684.6 linkuse as main transcript	c.692G>A	p.Ser231Asn	missense_variant	4/11	ENST00000282470.11
SPARCL1	NM_001128310.3 linkuse as main transcript	c.692G>A	p.Ser231Asn	missense_variant	5/12
SPARCL1	NM_001291976.2 linkuse as main transcript	c.317G>A	p.Ser106Asn	missense_variant	5/12
SPARCL1	NM_001291977.2 linkuse as main transcript	c.317G>A	p.Ser106Asn	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARCL1	ENST00000282470.11 linkuse as main transcript	c.692G>A	p.Ser231Asn	missense_variant	4/11	1	NM_004684.6	P2	Q14515-1
SPARCL1	ENST00000418378.5 linkuse as main transcript	c.692G>A	p.Ser231Asn	missense_variant	5/12	5		P2	Q14515-1
SPARCL1	ENST00000503414.5 linkuse as main transcript	c.317G>A	p.Ser106Asn	missense_variant	5/12	2		A2	Q14515-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Dec 14, 2023

The c.692G>A (p.S231N) 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 692, causing the serine (S) at amino acid position 231 to be replaced by an asparagine (N). 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

0.072

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

Cadd

Benign

1.7

Dann

Benign

0.94

DEOGEN2

Benign

0.049

T;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.021

M_CAP

Benign

0.0079

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.027

Sift

Benign

0.069

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0060

B;B;.

Vest4

0.045

MutPred

0.14

Gain of relative solvent accessibility (P = 0.0104);Gain of relative solvent accessibility (P = 0.0104);.;

MVP

0.030

MPC

0.076

ClinPred

0.098

GERP RS

2.0

Varity_R

0.038

gMVP

0.029

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