8-143559981-GAGGGCAGGGC-GAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC

Variant names:

• chr8-143559981-G-GAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC
• rs59118283
• NM_024736.7:c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC

Variant summary

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

The NM_024736.7(GSDMD):​c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,512 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GSDMD NM_024736.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 0 publications found

Genes affected

GSDMD (HGNC:25697): (gasdermin D) Gasdermin D is a member of the gasdermin family. Members of this family appear to play a role in regulation of epithelial proliferation. Gasdermin D has been suggested to act as a tumor suppressor. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024736.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMD	NM_024736.7	MANE Select	c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC		intron	N/A	NP_079012.3
	GSDMD	NM_001166237.1		c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC		intron	N/A	NP_001159709.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMD	ENST00000262580.9	TSL:1 MANE Select	c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC		intron	N/A	ENSP00000262580.4
	GSDMD	ENST00000533063.5	TSL:1	c.554+32_554+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC		intron	N/A	ENSP00000433958.1
	GSDMD	ENST00000524846.5	TSL:2	n.1089_1090insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436512 Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1 AN XY: 715474

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32814

American (AMR) AF: 0.00 AC: 0 AN: 43604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25718

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.00 AC: 0 AN: 84712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1093228

Other (OTH) AF: 0.00 AC: 0 AN: 59464

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs59118283; hg19: chr8-144642151;