Variant 19-43733373-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000270066.11(SMG9):c.1290G>A(p.Leu430=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,614,076 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 28 hom. )

Consequence

SMG9
ENST00000270066.11 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.278

Variant links:

Genes affected

SMG9 (HGNC:25763): (SMG9 nonsense mediated mRNA decay factor) This gene encodes a regulatory subunit of the SMG1 complex, which plays a critical role in nonsense-mediated mRNA decay (NMD). Binding of the encoded protein to the SMG1 complex kinase scaffold protein results in the inhibition of its kinase activity. Mutations in this gene cause a multiple congenital anomaly syndrome in human patients, characterized by brain malformation, congenital heart disease and other features. [provided by RefSeq, Jul 2016]

SMG9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 19-43733373-C-T is Benign according to our data. Variant chr19-43733373-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.278 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.004 (609/152206) while in subpopulation SAS AF= 0.0106 (51/4810). AF 95% confidence interval is 0.00828. There are 1 homozygotes in gnomad4. There are 294 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG9	NM_019108.4 linkuse as main transcript	c.1290G>A	p.Leu430=	synonymous_variant	12/14	ENST00000270066.11	NP_061981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG9	ENST00000270066.11 linkuse as main transcript	c.1290G>A	p.Leu430=	synonymous_variant	12/14	1	NM_019108.4	ENSP00000270066	P1	Q9H0W8-1
SMG9	ENST00000601170.5 linkuse as main transcript	c.1290G>A	p.Leu430=	synonymous_variant	12/13	2		ENSP00000471398		Q9H0W8-2
SMG9	ENST00000594081.1 linkuse as main transcript	n.534G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00402

AC:

611

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00845

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00439

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00451

AC:

1135

AN:

251480

Hom.:

AF XY:

0.00478

AC XY:

650

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00448

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00934

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00446

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00504

AC:

7366

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

3817

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00893

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.00505

Gnomad4 OTH exome

AF:

0.00584

GnomAD4 genome

AF:

0.00400

AC:

609

AN:

152206

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00844

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00473

Hom.:

Bravo

AF:

0.00421

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00575

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	SMG9: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.2

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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