NM_001165958.2:c.910G>T

Variant names:

• chr17-39905964-C-A
• NM_001165958.2:c.910G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001165958.2(GSDMB):​c.910G>T​(p.Gly304Trp) 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. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G304R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSDMB NM_001165958.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

Genes affected

GSDMB (HGNC:23690): (gasdermin B) This gene encodes a member of the gasdermin-domain containing protein family. Other gasdermin-family genes are implicated in the regulation of apoptosis in epithelial cells, and are linked to cancer. Alternative splicing and the use of alternative promoters results in multiple transcript variants. Additional variants have been described, but they are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31974566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.910G>T	p.Gly304Trp	missense_variant	Exon 9 of 11	ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.910G>T	p.Gly304Trp	missense_variant	Exon 9 of 11	5	NM_001165958.2	ENSP00000415049.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.96
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.64	.;T;.;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.7	.;D;D;.;D;D
REVEL	Benign	0.091
Sift	Uncertain	0.0010	.;D;D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;.;D
Vest4		0.45
MVP		0.14
MPC		0.63
ClinPred		0.96	D
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-38062217;