NM_178171.5:c.18T>A

Variant names:

• chr17-39965705-T-A
• rs994591687
• NM_178171.5:c.18T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178171.5(GSDMA):​c.18T>A​(p.Asn6Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GSDMA NM_178171.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.727
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18396601).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178171.5. 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
	GSDMA	NM_178171.5	MANE Select	c.18T>A	p.Asn6Lys	missense	Exon 2 of 12	NP_835465.2	Q96QA5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.18T>A	p.Asn6Lys	missense	Exon 2 of 12	ENSP00000301659.4	Q96QA5
	GSDMA	ENST00000635792.1	TSL:5	c.18T>A	p.Asn6Lys	missense	Exon 2 of 12	ENSP00000490739.1	Q96QA5
	GSDMA	ENST00000577447.1	TSL:4	c.18T>A	p.Asn6Lys	missense	Exon 2 of 4	ENSP00000461985.1	J3KRG2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455422 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 723392

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 43744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39416

South Asian (SAS) AF: 0.00 AC: 0 AN: 84850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109184

Other (OTH) AF: 0.00 AC: 0 AN: 60166

GnomAD4 genome Cov.: 31

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	Benign	0.25
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.35	N
PhyloP100		0.73
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.059
Sift	Benign	0.15	T
Sift4G	Uncertain	0.035	D
Polyphen		0.80	P
Vest4		0.64
MutPred		0.50		Gain of MoRF binding (P = 0.0068)
MVP		0.12
MPC		0.40
ClinPred		0.51	D
GERP RS		1.8
PromoterAI		-0.024	Neutral
Varity_R		0.060
gMVP		0.36
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs994591687; hg19: chr17-38121958;