Variant 1-156253053-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015327.3(SMG5):c.2528G>A(p.Ser843Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,030 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: 0.0000021 ( 0 hom. )

Consequence

SMG5
NM_015327.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

Variant links:

Genes affected

SMG5 (HGNC:24644): (SMG5 nonsense mediated mRNA decay factor) SMG5 is involved in nonsense-mediated mRNA decay (Ohnishi et al., 2003 [PubMed 14636577]).[supplied by OMIM, Mar 2008]

SMG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2523117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMG5	NM_015327.3 linkuse as main transcript	c.2528G>A	p.Ser843Asn	missense_variant	18/22	ENST00000361813.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMG5	ENST00000361813.5 linkuse as main transcript	c.2528G>A	p.Ser843Asn	missense_variant	18/22	1	NM_015327.3	P1
SMG5	ENST00000468993.1 linkuse as main transcript	n.340G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000820

AC:

AN:

243814

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131926

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458030

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724894

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000950

Hom.:

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

Oct 05, 2021

The c.2528G>A (p.S843N) alteration is located in exon 18 (coding exon 18) of the SMG5 gene. This alteration results from a G to A substitution at nucleotide position 2528, causing the serine (S) at amino acid position 843 to be replaced by an asparagine (N). 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

0.68

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

M_CAP

Benign

0.011

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.91

REVEL

Benign

0.14

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.012

Polyphen

0.052

Vest4

0.56

MutPred

0.12

Loss of phosphorylation at S843 (P = 0.0464);

MVP

0.35

MPC

0.27

ClinPred

0.39

GERP RS

6.1

Varity_R

0.26

gMVP

0.45

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