chr17-2243997-T-C

Variant names:

• chr17-2243997-T-C
• rs216219
• NM_017575.5:c.2723+661A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017575.5(SMG6):​c.2723+661A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,938 control chromosomes in the GnomAD database, including 26,584 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 0.58 (26584 hom., cov: 31)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 28 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 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.2723+661A>G		intron	N/A	NP_060045.4
	SMG6	NM_001256827.2		c.-2+661A>G		intron	N/A	NP_001243756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	ENST00000263073.11	TSL:1 MANE Select	c.2723+661A>G		intron	N/A	ENSP00000263073.5
	SMG6	ENST00000354901.8	TSL:1	c.-2+661A>G		intron	N/A	ENSP00000346977.4
	SMG6	ENST00000570659.5	TSL:4	c.-2+661A>G		intron	N/A	ENSP00000460898.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87803 AN: 151820 Hom.: 26571 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.578 AC: 87857 AN: 151938 Hom.: 26584 Cov.: 31 AF XY: 0.583 AC XY: 43249 AN XY: 74246

African (AFR) AF: 0.391 AC: 16184 AN: 41422

American (AMR) AF: 0.618 AC: 9433 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2357 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3861 AN: 5134

South Asian (SAS) AF: 0.633 AC: 3043 AN: 4806

European-Finnish (FIN) AF: 0.669 AC: 7070 AN: 10562

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43902 AN: 67962

Other (OTH) AF: 0.595 AC: 1254 AN: 2108

Alfa AF: 0.626 Hom.: 90676

Bravo AF: 0.565

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.39
PhyloP100		-0.63
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: rs216219; hg19: chr17-2147291;