Variant rs13051 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004684.6(SPARCL1):c.146C>A(p.Ala49Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,608,716 control chromosomes in the GnomAD database, including 140,871 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.51 ( 22817 hom., cov: 33)

Exomes 𝑓: 0.39 ( 118054 hom. )

Consequence

SPARCL1
NM_004684.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.951

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.185086E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPARCL1	NM_004684.6 linkuse as main transcript	c.146C>A	p.Ala49Asp	missense_variant	3/11	ENST00000282470.11
SPARCL1	NM_001128310.3 linkuse as main transcript	c.146C>A	p.Ala49Asp	missense_variant	4/12
SPARCL1	NM_001291976.2 linkuse as main transcript	c.-230C>A		5_prime_UTR_variant	4/12
SPARCL1	NM_001291977.2 linkuse as main transcript	c.-141-471C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARCL1	ENST00000282470.11 linkuse as main transcript	c.146C>A	p.Ala49Asp	missense_variant	3/11	1	NM_004684.6	P2	Q14515-1

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77955

AN:

152022

Hom.:

22774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.496

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.491

GnomAD3 exomes

AF:

0.449

AC:

112080

AN:

249676

Hom.:

27137

AF XY:

0.444

AC XY:

59942

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.820

Gnomad AMR exome

AF:

0.498

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.430

Gnomad SAS exome

AF:

0.563

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.392

AC:

570514

AN:

1456576

Hom.:

118054

Cov.:

AF XY:

0.396

AC XY:

286965

AN XY:

724788

show subpopulations

Gnomad4 AFR exome

AF:

0.821

Gnomad4 AMR exome

AF:

0.493

Gnomad4 ASJ exome

AF:

0.450

Gnomad4 EAS exome

AF:

0.395

Gnomad4 SAS exome

AF:

0.562

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.358

Gnomad4 OTH exome

AF:

0.429

GnomAD4 genome

AF:

0.513

AC:

78052

AN:

152140

Hom.:

22817

Cov.:

AF XY:

0.515

AC XY:

38305

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.805

Gnomad4 AMR

AF:

0.496

Gnomad4 ASJ

AF:

0.452

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.395

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.495

Alfa

AF:

0.393

Hom.:

19777

Bravo

AF:

0.531

TwinsUK

AF:

0.357

AC:

1325

ALSPAC

AF:

0.357

AC:

1377

ESP6500AA

AF:

0.807

AC:

3556

ESP6500EA

AF:

0.372

AC:

3196

ExAC

AF:

0.457

AC:

55427

Asia WGS

AF:

0.567

AC:

1971

AN:

3478

EpiCase

AF:

0.372

EpiControl

AF:

0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.4

DANN

Benign

0.17

DEOGEN2

Benign

0.019

T;T;.;.;T;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.26

.;T;T;T;T;T;T;T

MetaRNN

Benign

9.2e-7

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.1

N;N;.;.;.;.;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

1.4

N;N;N;N;N;N;N;N

REVEL

Benign

0.093

Sift

Benign

0.93

T;T;T;T;T;T;T;T

Sift4G

Benign

0.74

T;T;.;.;.;T;T;.

Polyphen

0.0

B;B;.;.;.;.;.;.

Vest4

0.038

MPC

0.12

ClinPred

0.00023

GERP RS

3.0

Varity_R

0.062

gMVP

0.085

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over