17-2214651-A-G

Variant names:

• chr17-2214651-A-G
• rs2281727
• NM_017575.5:c.2869+21841T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 49 publications found

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]

ENSG00000236838 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017575.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	NM_017575.5	MANE Select	c.2869+21841T>C		intron	N/A	NP_060045.4
	SMG6	NM_001256827.2		c.145+21841T>C		intron	N/A	NP_001243756.1
	SMG6	NM_001256828.1		c.145+21841T>C		intron	N/A	NP_001243757.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	ENST00000263073.11	TSL:1 MANE Select	c.2869+21841T>C		intron	N/A	ENSP00000263073.5
	SMG6	ENST00000354901.8	TSL:1	c.145+21841T>C		intron	N/A	ENSP00000346977.4
	SMG6	ENST00000536871.6	TSL:2	c.145+21841T>C		intron	N/A	ENSP00000440283.2

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

African (AFR) AF: 0.439 AC: 18196 AN: 41444

American (AMR) AF: 0.360 AC: 5511 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1360 AN: 5172

South Asian (SAS) AF: 0.377 AC: 1818 AN: 4818

European-Finnish (FIN) AF: 0.341 AC: 3605 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24163 AN: 67988

Other (OTH) AF: 0.379 AC: 801 AN: 2112

Alfa AF: 0.354 Hom.: 21338

Bravo AF: 0.382

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		0.66
PromoterAI		-0.0064	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2281727; hg19: chr17-2117945;