17-2240166-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017575.5(SMG6):c.2724-3529C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,016 control chromosomes in the GnomAD database, including 14,749 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 0.42 (14747 hom., cov: 32)
  • Exomes 𝑓: 0.40 (2 hom.)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMG6	NM_017575.5	c.2724-3529C>A		intron_variant		ENST00000263073.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMG6	ENST00000263073.11	c.2724-3529C>A		intron_variant		1	NM_017575.5	P1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64188 AN: 151886 Hom.: 14729 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.400 AC: 4 AN: 10 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.423 AC: 64252 AN: 152006 Hom.: 14747 Cov.: 32 AF XY: 0.419 AC XY: 31096 AN XY: 74298

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.406

Alfa AF: 0.345 Hom.: 10540

Bravo AF: 0.436

Asia WGS AF: 0.332 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	10
Dann	Benign	0.59

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: rs10852932; hg19: chr17-2143460;