Variant 17-2303674-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_017575.5(SMG6):c.47G>A(p.Arg16His) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,343,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

SMG6
NM_017575.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42

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:

SRR (HGNC:14398): (serine racemase) Enables several functions, including L-serine ammonia-lyase activity; PDZ domain binding activity; and anion binding activity. Involved in pyruvate biosynthetic process; response to lipopolysaccharide; and serine family amino acid metabolic process. Located in cytoplasm and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

SRR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32453743).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG6	NM_017575.5 linkuse as main transcript	c.47G>A	p.Arg16His	missense_variant	1/19	ENST00000263073.11	NP_060045.4	Q86US8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11 linkuse as main transcript	c.47G>A	p.Arg16His	missense_variant	1/19	1	NM_017575.5	ENSP00000263073.5		Q86US8-1
SRR	ENST00000572709.5 linkuse as main transcript	c.-5+197C>T		intron_variant		1		ENSP00000458814.1		Q3ZK31

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000744

AC:

AN:

1343376

Hom.:

Cov.:

AF XY:

0.00000604

AC XY:

AN XY:

662360

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000942

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.47G>A (p.R16H) alteration is located in exon 1 (coding exon 1) of the SMG6 gene. This alteration results from a G to A substitution at nucleotide position 47, causing the arginine (R) at amino acid position 16 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.17

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.038

Polyphen

1.0

Vest4

0.15

MutPred

0.32

Loss of MoRF binding (P = 0.0038);

MVP

0.36

MPC

0.73

ClinPred

0.98

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.38

gMVP

0.48

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over