Variant chr8-14090486-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139167.4(SGCZ):c.896G>A(p.Gly299Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,612,868 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

SGCZ
NM_139167.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

Variant links:

Genes affected

SGCZ (HGNC:14075): (sarcoglycan zeta) The zeta-sarcoglycan gene measures over 465 kb and localizes to 8p22. This protein is part of the sarcoglycan complex, a group of 6 proteins. The sarcoglycans are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a carboxyl-terminal cluster with several conserved cysteine residues. The sarcoglycan complex is part of the dystrophin-associated glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extra-cellular matrix. [provided by RefSeq, Jul 2008]

SGCZ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13560838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SGCZ	NM_139167.4 linkuse as main transcript	c.896G>A	p.Gly299Asp	missense_variant	8/8	ENST00000382080.6
SGCZ	NM_001322879.2 linkuse as main transcript	c.794G>A	p.Gly265Asp	missense_variant	7/7
SGCZ	NM_001322880.2 linkuse as main transcript	c.773G>A	p.Gly258Asp	missense_variant	7/7
SGCZ	NM_001322881.2 linkuse as main transcript	c.551G>A	p.Gly184Asp	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCZ	ENST00000382080.6 linkuse as main transcript	c.896G>A	p.Gly299Asp	missense_variant	8/8	5	NM_139167.4	P1	Q96LD1-2
SGCZ	ENST00000421524.6 linkuse as main transcript	c.755G>A	p.Gly252Asp	missense_variant	6/6	1

Frequencies

GnomAD3 genomes

AF:

0.000290

AC:

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

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:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000758

AC:

AN:

250568

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.000740

Gnomad AMR exome

AF:

0.000174

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:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1460884

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.000808

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000290

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.000918

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000129

Hom.:

Bravo

AF:

0.000355

ExAC

AF:

0.0000906

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

Feb 10, 2023

The c.896G>A (p.G299D) alteration is located in exon 8 (coding exon 8) of the SGCZ gene. This alteration results from a G to A substitution at nucleotide position 896, causing the glycine (G) at amino acid position 299 to be replaced by an aspartic acid (D). 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

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.15

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.14

T;T

MetaSVM

Pathogenic

0.82

MutationTaster

Benign

0.88

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.93

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.095

T;T

Sift4G

Benign

0.087

T;T

Polyphen

0.74

P;P

Vest4

0.24

MVP

0.82

MPC

0.016

ClinPred

0.050

GERP RS

4.6

gMVP

0.39

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