Variant 4-87480385-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004684.6(SPARCL1):c.1804C>T(p.His602Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000542 in 1,604,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

SPARCL1
NM_004684.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.55

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPARCL1	NM_004684.6 linkuse as main transcript	c.1804C>T	p.His602Tyr	missense_variant	9/11	ENST00000282470.11
SPARCL1	NM_001128310.3 linkuse as main transcript	c.1804C>T	p.His602Tyr	missense_variant	10/12
SPARCL1	NM_001291976.2 linkuse as main transcript	c.1429C>T	p.His477Tyr	missense_variant	10/12
SPARCL1	NM_001291977.2 linkuse as main transcript	c.1429C>T	p.His477Tyr	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPARCL1	ENST00000282470.11 linkuse as main transcript	c.1804C>T	p.His602Tyr	missense_variant	9/11	1	NM_004684.6	P2	Q14515-1
SPARCL1	ENST00000418378.5 linkuse as main transcript	c.1804C>T	p.His602Tyr	missense_variant	10/12	5		P2	Q14515-1
SPARCL1	ENST00000503414.5 linkuse as main transcript	c.1429C>T	p.His477Tyr	missense_variant	10/12	2		A2	Q14515-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000447

AC:

AN:

246086

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133078

show subpopulations

Gnomad AFR exome

AF:

0.0000631

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:

0.0000802

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000551

AC:

AN:

1452192

Hom.:

Cov.:

AF XY:

0.0000609

AC XY:

AN XY:

722230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

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:

0.0000686

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000576

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

Mar 11, 2024

The c.1804C>T (p.H602Y) alteration is located in exon 10 (coding exon 8) of the SPARCL1 gene. This alteration results from a C to T substitution at nucleotide position 1804, causing the histidine (H) at amino acid position 602 to be replaced by a tyrosine (Y). 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

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Uncertain

-0.010

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.56

D;D;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.5

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.78

MVP

0.50

MPC

0.47

ClinPred

0.82

GERP RS

5.3

Varity_R

0.57

gMVP

0.76

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