8-129751548-A-T

Variant names:

• chr8-129751548-A-T
• NM_031415.3:c.937T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031415.3(GSDMC):​c.937T>A​(p.Trp313Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSDMC NM_031415.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.19
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056450605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031415.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMC	NM_031415.3	MANE Select	c.937T>A	p.Trp313Arg	missense	Exon 10 of 14	NP_113603.1	Q9BYG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMC	ENST00000276708.9	TSL:1 MANE Select	c.937T>A	p.Trp313Arg	missense	Exon 10 of 14	ENSP00000276708.4	Q9BYG8
	GSDMC	ENST00000522273.5	TSL:1	n.282T>A		non_coding_transcript_exon	Exon 4 of 8
	GSDMC	ENST00000521365.1	TSL:3	n.*160T>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.012
DANN	Benign	0.26
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.49	N
PhyloP100		-3.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.016
Sift	Benign	0.63	T
Sift4G	Benign	0.58	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.54		Gain of disorder (P = 0.0081)
MVP		0.014
MPC		0.022
ClinPred		0.054	T
GERP RS		-7.7
Varity_R		0.052
gMVP		0.16
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr8-130763794;