17-39905943-G-C

Variant names:

• chr17-39905943-G-C
• rs2305480
• NM_001165958.2:c.931C>G
• GSDMB p.Pro311Ala

GermlineCancer (beta)

Variant summary

Our verdict is

Uncertain significance

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 0 classification points (ACMG Germline Pathogenicity v2019): 2P and 2B. PM2BP4_Moderate

The NM_001165958.2(GSDMB):c.931C>G (p.Pro311Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSDMB NM_001165958.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 0 publications found

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]

Classification according to ACMG Germline Pathogenicity v2019

Our verdict: Uncertain_significance. The variant received 0 points.

• PM2: Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
• BP4: Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001165958.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMB	NM_001165958.2	MANE Select	c.931C>G	p.Pro311Ala	missense	Exon 9 of 11	NP_001159430.1	Q8TAX9-4
	GSDMB	NM_001388420.1		c.931C>G	p.Pro311Ala	missense	Exon 8 of 10	NP_001375349.1	Q8TAX9-4
	GSDMB	NM_001165959.2		c.904C>G	p.Pro302Ala	missense	Exon 8 of 10	NP_001159431.1	Q8TAX9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMB	ENST00000418519.6	TSL:5 MANE Select	c.931C>G	p.Pro311Ala	missense	Exon 9 of 11	ENSP00000415049.1	Q8TAX9-4
	GSDMB	ENST00000360317.7	TSL:1	c.931C>G	p.Pro311Ala	missense	Exon 8 of 10	ENSP00000353465.3	Q8TAX9-4
	GSDMB	ENST00000394179.5	TSL:1	c.892C>G	p.Pro298Ala	missense	Exon 7 of 9	ENSP00000377733.2	Q8TAX9-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.0
DANN	Benign	0.75
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.43
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.11
Sift	Benign	0.73	T
Sift4G	Benign	0.24	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.14

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2305480;

hg19: chr17-38062196;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar