Genetic Variant SPARCL1:p.Gly402Glu (chr4-87493595-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G402A) has been classified 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

Publications

0 publications found

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 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

SPARCL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08406106).

BS2

High AC in GnomAdExome4 at 21 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPARCL1	NM_004684.6	MANE Select	c.1205G>A	p.Gly402Glu	missense	Exon 4 of 11	NP_004675.3
SPARCL1	NM_001128310.3		c.1205G>A	p.Gly402Glu	missense	Exon 5 of 12	NP_001121782.1	Q14515-1
SPARCL1	NM_001291976.2		c.830G>A	p.Gly277Glu	missense	Exon 5 of 12	NP_001278905.1	Q14515-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPARCL1	ENST00000282470.11	TSL:1 MANE Select	c.1205G>A	p.Gly402Glu	missense	Exon 4 of 11	ENSP00000282470.6	Q14515-1
SPARCL1	ENST00000946054.1		c.1205G>A	p.Gly402Glu	missense	Exon 4 of 11	ENSP00000616113.1
SPARCL1	ENST00000880794.1		c.1205G>A	p.Gly402Glu	missense	Exon 4 of 11	ENSP00000550853.1

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

GnomAD2 exomes

AF:

0.00000808

AC:

AN:

247442

AF XY:

0.0000149

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 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

African (AFR)

AF:

0.0000301

AC:

AN:

33184

American (AMR)

AF:

0.00

AC:

AN:

43854

Ashkenazi Jewish (ASJ)

AF:

0.0000387

AC:

AN:

25822

East Asian (EAS)

AF:

0.00

AC:

AN:

39552

South Asian (SAS)

AF:

0.00

AC:

AN:

85796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1108266

Other (OTH)

AF:

0.0000166

AC:

AN:

60122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.85

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.035

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.61

M_CAP

Benign

0.068

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.0

PhyloP100

-0.26

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.060

REVEL

Uncertain

0.30

Sift

Benign

0.099

Sift4G

Benign

1.0

Polyphen

0.96

Vest4

0.093

MutPred

0.25

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

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over