Variant 4-87493670-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000282470.11(SPARCL1):c.1130T>C(p.Ile377Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SPARCL1
ENST00000282470.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0910

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:

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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=0.066123426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPARCL1	NM_004684.6 linkuse as main transcript	c.1130T>C	p.Ile377Thr	missense_variant	4/11	ENST00000282470.11	NP_004675.3
SPARCL1	NM_001128310.3 linkuse as main transcript	c.1130T>C	p.Ile377Thr	missense_variant	5/12		NP_001121782.1
SPARCL1	NM_001291976.2 linkuse as main transcript	c.755T>C	p.Ile252Thr	missense_variant	5/12		NP_001278905.1
SPARCL1	NM_001291977.2 linkuse as main transcript	c.755T>C	p.Ile252Thr	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.1130T>C	p.Ile377Thr	missense_variant	4/11	1	NM_004684.6	ENSP00000282470	P2	Q14515-1
SPARCL1	ENST00000418378.5 linkuse as main transcript	c.1130T>C	p.Ile377Thr	missense_variant	5/12	5		ENSP00000414856	P2	Q14515-1
SPARCL1	ENST00000503414.5 linkuse as main transcript	c.755T>C	p.Ile252Thr	missense_variant	5/12	2		ENSP00000422903	A2	Q14515-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251114

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

May 17, 2023

The c.1130T>C (p.I377T) alteration is located in exon 5 (coding exon 3) of the SPARCL1 gene. This alteration results from a T to C substitution at nucleotide position 1130, causing the isoleucine (I) at amino acid position 377 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

0.081

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.1

DANN

Benign

0.51

DEOGEN2

Benign

0.079

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.57

.;T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.025

D;D;D

Sift4G

Benign

0.77

T;T;T

Polyphen

0.45

P;P;.

Vest4

0.085

MutPred

0.43

Gain of glycosylation at I377 (P = 0.0299);Gain of glycosylation at I377 (P = 0.0299);.;

MVP

0.23

MPC

0.11

ClinPred

0.049

GERP RS

-6.6

Varity_R

0.049

gMVP

0.080

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