SMG8 p.Ala14Ala

Variant names:

• chr17-59210090-A-A
• ENST00000300917.10:c.

Your query was ambiguous. Multiple possible variants found:

• chr17-59210091--
• chr17-59210093-A-T
• chr17-59210093-A-C
• chr17-59210093-A-G

Variant summary

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

The ENST00000300917.10(SMG8):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMG8 ENST00000300917.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• Publications: 0 publications found

Genes affected

SMG8 (HGNC:25551): (SMG8 nonsense mediated mRNA decay factor) Involved in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay and regulation of protein kinase activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SMG8 Gene-Disease associations (from GenCC):

• Alzahrani-Kuwahara syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000265303 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000300917.10. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG8	ENST00000300917.10	TSL:1 MANE Select	c.		intron	N/A	ENSP00000300917.4	Q8ND04-1
	ENSG00000265303	ENST00000577660.1	TSL:3	c.		intron	N/A	ENSP00000464167.1	J3QRE1
	SMG8	ENST00000543872.6	TSL:5	c.		intron	N/A	ENSP00000438748.2	Q8ND04-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

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

hg19: chr17-57287451;