rs216193

chr17-2300159-A-Gchr17-2300159-A-T

Variant summary

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

The NM_017575.5(SMG6):c.594T>C(p.Ala198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,613,554 control chromosomes in the GnomAD database, including 305,590 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 0.56 (24567 hom., cov: 31)
  • Exomes 𝑓: 0.62 (281023 hom.)
• Consequence: SMG6 NM_017575.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

Genes affected

SMG6 (HGNC:17809): (SMG6 nonsense mediated mRNA decay factor) This gene encodes a component of the telomerase ribonucleoprotein complex responsible for the replication and maintenance of chromosome ends. The encoded protein also plays a role in the nonsense-mediated mRNA decay (NMD) pathway, providing the endonuclease activity near the premature translation termination codon that is needed to initiate NMD. Alternatively spliced transcript variants encoding distinct protein isoforms have been described. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-0.437 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMG6	NM_017575.5	c.594T>C	p.Ala198=	synonymous_variant	2/19	ENST00000263073.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMG6	ENST00000263073.11	c.594T>C	p.Ala198=	synonymous_variant	2/19	1	NM_017575.5	P1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84821 AN: 151598 Hom.: 24552 Cov.: 31

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.572

GnomAD3 exomes AF: 0.609 AC: 153027 AN: 251412 Hom.: 47359 AF XY: 0.609 AC XY: 82808 AN XY: 135884

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.655

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.682

Gnomad SAS exome AF: 0.564

Gnomad FIN exome AF: 0.635

Gnomad NFE exome AF: 0.615

Gnomad OTH exome AF: 0.609

GnomAD4 exome AF: 0.617 AC: 902565 AN: 1461834 Hom.: 281023 Cov.: 88 AF XY: 0.616 AC XY: 447729 AN XY: 727214

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.725

Gnomad4 SAS exome AF: 0.570

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.559 AC: 84879 AN: 151720 Hom.: 24567 Cov.: 31 AF XY: 0.564 AC XY: 41798 AN XY: 74142

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.571

Alfa AF: 0.599 Hom.: 36711

Bravo AF: 0.551

Asia WGS AF: 0.566 AC: 1967 AN: 3478

EpiCase AF: 0.617

EpiControl AF: 0.611

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.54
Dann	Benign	0.56

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: rs216193; hg19: chr17-2203453; COSMIC: COSV53963167; COSMIC: COSV53963167;