Variant 16-18863720-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015092.5(SMG1):c.3625G>T(p.Ala1209Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,589,540 control chromosomes in the GnomAD database, including 764 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 71 hom., cov: 32)

Exomes 𝑓: 0.029 ( 693 hom. )

Consequence

SMG1
NM_015092.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

SMG1 (HGNC:30045): (SMG1 nonsense mediated mRNA decay associated PI3K related kinase) This gene encodes a protein involved in nonsense-mediated mRNA decay (NMD) as part of the mRNA surveillance complex. The protein has kinase activity and is thought to function in NMD by phosphorylating the regulator of nonsense transcripts 1 protein. Alternatively spliced transcript variants have been described, but their full-length nature has yet to be determined. [provided by RefSeq, Mar 2013]

SMG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001909405).

BP6

Variant 16-18863720-C-A is Benign according to our data. Variant chr16-18863720-C-A is described in ClinVar as [Benign]. Clinvar id is 773577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG1	NM_015092.5 linkuse as main transcript	c.3625G>T	p.Ala1209Ser	missense_variant	25/63	ENST00000446231.7	NP_055907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG1	ENST00000446231.7 linkuse as main transcript	c.3625G>T	p.Ala1209Ser	missense_variant	25/63	1	NM_015092.5	ENSP00000402515	P1	Q96Q15-1
SMG1	ENST00000565324.5 linkuse as main transcript	c.3295G>T	p.Ala1099Ser	missense_variant	23/61	1		ENSP00000456259
SMG1	ENST00000563235.5 linkuse as main transcript	c.1918G>T	p.Ala640Ser	missense_variant	13/17	2		ENSP00000455861

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4075

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00980

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0433

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0266

AC:

6163

AN:

231482

Hom.:

AF XY:

0.0276

AC XY:

3525

AN XY:

127696

show subpopulations

Gnomad AFR exome

AF:

0.00738

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0500

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0168

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.0343

Gnomad OTH exome

AF:

0.0377

GnomAD4 exome

AF:

0.0292

AC:

41939

AN:

1437268

Hom.:

693

Cov.:

AF XY:

0.0290

AC XY:

20769

AN XY:

715838

show subpopulations

Gnomad4 AFR exome

AF:

0.00815

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0490

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0346

Gnomad4 NFE exome

AF:

0.0313

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0268

AC:

4077

AN:

152272

Hom.:

Cov.:

AF XY:

0.0266

AC XY:

1981

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00977

Gnomad4 AMR

AF:

0.0309

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0433

Gnomad4 NFE

AF:

0.0353

Gnomad4 OTH

AF:

0.0327

Alfa

AF:

0.0181

Hom.:

Bravo

AF:

0.0257

ESP6500AA

AF:

0.00969

AC:

ESP6500EA

AF:

0.0351

AC:

142

ExAC

AF:

0.0262

AC:

2999

EpiCase

AF:

0.0396

EpiControl

AF:

0.0397

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.41

N;.

REVEL

Benign

0.057

Sift

Benign

0.88

T;.

Polyphen

0.0010

B;.

Vest4

0.076

MPC

1.8

ClinPred

0.015

GERP RS

4.8

Varity_R

0.14

gMVP

0.13

Splicing

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