Genetic Variant NM_139167.4:c.40-295695T>C (chr8-14850621-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_139167.4(SGCZ):c.40-295695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 152,318 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.016 ( 42 hom., cov: 32)

Consequence

SGCZ
NM_139167.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0280

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0155 (2363/152318) while in subpopulation AFR AF = 0.0402 (1669/41564). AF 95% confidence interval is 0.0386. There are 42 homozygotes in GnomAd4. There are 1148 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4 link	c.40-295695T>C	intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2	Q96LD1-2
SGCZ	NM_001322879.2 link	c.40-295695T>C	intron_variant	Intron 1 of 6		NP_001309808.1	Q96LD1Q08AT0
SGCZ	NM_001322880.2 link	c.40-295695T>C	intron_variant	Intron 1 of 6		NP_001309809.1	Q96LD1
SGCZ	NM_001322881.2 link	c.-89-295695T>C	intron_variant	Intron 1 of 6		NP_001309810.1	Q96LD1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6 link	c.40-295695T>C		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1		Q96LD1-2

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2354

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0402

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00620

Gnomad OTH

AF:

0.0119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0155

AC:

2363

AN:

152318

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1148

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0402

AC:

1669

AN:

41564

American (AMR)

AF:

0.00562

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00232

AC:

AN:

5174

South Asian (SAS)

AF:

0.0178

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00490

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00620

AC:

422

AN:

68030

Other (OTH)

AF:

0.0118

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

109

219

328

438

547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0142

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.5

(source)

DANN

Benign

0.51

PhyloP100

0.028

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over