Variant chr8-14090583-A-G 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.799T>C(p.Ser267Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,612,866 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 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

SGCZ
NM_139167.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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=0.069738925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SGCZ	NM_139167.4 linkuse as main transcript	c.799T>C	p.Ser267Pro	missense_variant	8/8	ENST00000382080.6
SGCZ	NM_001322879.2 linkuse as main transcript	c.697T>C	p.Ser233Pro	missense_variant	7/7
SGCZ	NM_001322880.2 linkuse as main transcript	c.676T>C	p.Ser226Pro	missense_variant	7/7
SGCZ	NM_001322881.2 linkuse as main transcript	c.454T>C	p.Ser152Pro	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCZ	ENST00000382080.6 linkuse as main transcript	c.799T>C	p.Ser267Pro	missense_variant	8/8	5	NM_139167.4	P1	Q96LD1-2
SGCZ	ENST00000421524.6 linkuse as main transcript	c.658T>C	p.Ser220Pro	missense_variant	6/6	1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000263

AC:

AN:

250922

Hom.:

AF XY:

0.000288

AC XY:

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000423

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000178

AC:

260

AN:

1460680

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000138

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000722

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:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000257

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000713

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

Aug 16, 2021

The c.799T>C (p.S267P) alteration is located in exon 8 (coding exon 8) of the SGCZ gene. This alteration results from a T to C substitution at nucleotide position 799, causing the serine (S) at amino acid position 267 to be replaced by a proline (P). 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

-0.52

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.67

N;N

REVEL

Benign

0.076

Sift

Benign

0.57

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.90

P;P

Vest4

0.16

MVP

0.17

MPC

0.0091

ClinPred

0.027

GERP RS

0.96

gMVP

0.26

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