17-39965896-C-T

Position:

• chr17-39965896-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178171.5(GSDMA):​c.209C>T​(p.Pro70Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSDMA NM_178171.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65

Genes affected

GSDMA (HGNC:13311): (gasdermin A) Predicted to enable phosphatidylinositol-4,5-bisphosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylserine binding activity. Involved in apoptotic process. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16698974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMA	NM_178171.5	c.209C>T	p.Pro70Leu	missense_variant	2/12	ENST00000301659.9
GSDMA	XM_006721832.4	c.209C>T	p.Pro70Leu	missense_variant	2/12
GSDMA	XM_017024502.3	c.209C>T	p.Pro70Leu	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMA	ENST00000301659.9	c.209C>T	p.Pro70Leu	missense_variant	2/12	1	NM_178171.5	P1
GSDMA	ENST00000635792.1	c.209C>T	p.Pro70Leu	missense_variant	2/12	5		P1
GSDMA	ENST00000577447.1	c.209C>T	p.Pro70Leu	missense_variant	2/4	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.209C>T (p.P70L) alteration is located in exon 2 (coding exon 1) of the GSDMA gene. This alteration results from a C to T substitution at nucleotide position 209, causing the proline (P) at amino acid position 70 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0036	T;T;T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.47	N
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L;L;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.56	T
Polyphen		0.54	P;P;.
Vest4		0.46
MutPred		0.45		Loss of glycosylation at P70 (P = 0.0437);Loss of glycosylation at P70 (P = 0.0437);Loss of glycosylation at P70 (P = 0.0437);
MVP		0.40
MPC		0.30
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.089
gMVP		0.24

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: chr17-38122149;