rs6503905

Positions:

• chr17-59210093-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018149.7(SMG8):​c.42A>G​(p.Ala14Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,577,986 control chromosomes in the GnomAD database, including 329,630 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (38597 hom., cov: 31)
  • Exomes 𝑓: 0.64 (291033 hom.)
• Consequence: SMG8 NM_018149.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

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]

ENSG00000265303 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-0.521 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG8	NM_018149.7	c.42A>G	p.Ala14Ala	synonymous_variant	1/4	ENST00000300917.10	NP_060619.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG8	ENST00000300917.10	c.42A>G	p.Ala14Ala	synonymous_variant	1/4	1	NM_018149.7	ENSP00000300917.4
ENSG00000265303	ENST00000577660.1	c.136-4712A>G		intron_variant		3		ENSP00000464167.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106446 AN: 151914 Hom.: 38536 Cov.: 31

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.677

GnomAD3 exomes AF: 0.619 AC: 135223 AN: 218524 Hom.: 42981 AF XY: 0.617 AC XY: 72675 AN XY: 117770

Gnomad AFR exome AF: 0.904

Gnomad AMR exome AF: 0.529

Gnomad ASJ exome AF: 0.645

Gnomad EAS exome AF: 0.458

Gnomad SAS exome AF: 0.601

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.630

Gnomad OTH exome AF: 0.618

GnomAD4 exome AF: 0.636 AC: 906221 AN: 1425954 Hom.: 291033 Cov.: 54 AF XY: 0.635 AC XY: 449042 AN XY: 707344

Gnomad4 AFR exome AF: 0.911

Gnomad4 AMR exome AF: 0.542

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.701 AC: 106561 AN: 152032 Hom.: 38597 Cov.: 31 AF XY: 0.696 AC XY: 51690 AN XY: 74294

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.680

Alfa AF: 0.652 Hom.: 36985

Bravo AF: 0.706

Asia WGS AF: 0.577 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.8
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

LitVar

Other links and lift over

dbSNP: rs6503905; hg19: chr17-57287454; COSMIC: COSV56283976; COSMIC: COSV56283976;