chr17-2214651-A-G

Position:

• chr17-2214651-A-G

Variant summary

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

The NM_017575.5(SMG6):​c.2869+21841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,064 control chromosomes in the GnomAD database, including 11,004 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 0.38 (11004 hom., cov: 31)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMG6	NM_017575.5	c.2869+21841T>C		intron_variant		ENST00000263073.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMG6	ENST00000263073.11	c.2869+21841T>C		intron_variant		1	NM_017575.5	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57014 AN: 151946 Hom.: 10991 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.381

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 57070 AN: 152064 Hom.: 11004 Cov.: 31 AF XY: 0.375 AC XY: 27842 AN XY: 74340

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.379

Alfa AF: 0.353 Hom.: 15070

Bravo AF: 0.382

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.78

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: rs2281727; hg19: chr17-2117945;