Genetic Variant GSDMC:p.Ala253Ala (chr8-129752783-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_031415.3(GSDMC):c.759G>A(p.Ala253Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,614,122 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 139 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 123 hom. )

Consequence

GSDMC
NM_031415.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.305

Variant links:

Genes affected

GSDMC (HGNC:7151): (gasdermin C) Predicted to enable phosphatidylinositol-4,5-bisphosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylserine binding activity. Predicted to be involved in defense response to bacterium and pyroptosis. Predicted to act upstream of or within intestinal epithelial cell development. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GSDMC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-129752783-C-T is Benign according to our data. Variant chr8-129752783-C-T is described in ClinVar as [Benign]. Clinvar id is 713508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.305 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMC	NM_031415.3 link	c.759G>A	p.Ala253Ala	synonymous_variant	Exon 7 of 14	ENST00000276708.9	NP_113603.1	Q9BYG8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GSDMC	ENST00000276708.9 link	c.759G>A	p.Ala253Ala	synonymous_variant	Exon 7 of 14	1	NM_031415.3	ENSP00000276708.4	Q9BYG8
GSDMC	ENST00000522273.5 link	n.104G>A		non_coding_transcript_exon_variant	Exon 1 of 8	1
GSDMC	ENST00000619643.1 link	c.759G>A	p.Ala253Ala	synonymous_variant	Exon 6 of 13	2			Q9BYG8
GSDMC	ENST00000521365.1 link	n.-26G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3307

AN:

152144

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0755

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00779

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00567

AC:

1412

AN:

248938

Hom.:

AF XY:

0.00409

AC XY:

551

AN XY:

134748

show subpopulations

Gnomad AFR exome

AF:

0.0788

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00219

AC:

3197

AN:

1461860

Hom.:

123

Cov.:

AF XY:

0.00185

AC XY:

1343

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0793

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.00485

GnomAD4 genome

AF:

0.0217

AC:

3311

AN:

152262

Hom.:

139

Cov.:

AF XY:

0.0210

AC XY:

1566

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0754

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.0250

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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