Variant rs216193 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017575.5(SMG6):c.594T>C(p.Ala198Ala) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.437

Variant links:

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]

SMG6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
SMG6	NM_017575.5 link	c.594T>C	p.Ala198Ala	synonymous_variant	2/19	ENST00000263073.11	NP_060045.4	Q86US8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11 link	c.594T>C	p.Ala198Ala	synonymous_variant	2/19	1	NM_017575.5	ENSP00000263073.5		Q86US8-1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

84821

AN:

151598

Hom.:

24552

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.616

AC XY:

447729

AN XY:

727214

show subpopulations

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.:

AF XY:

0.564

AC XY:

41798

AN XY:

74142

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over