19-43734429-T-G

Position:

• chr19-43734429-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The ENST00000270066.11(SMG9):​c.1062A>C​(p.Ser354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMG9 ENST00000270066.11 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.65

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-43734429-T-G is Benign according to our data. Variant chr19-43734429-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 727370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.65 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG9	NM_019108.4	c.1062A>C	p.Ser354=	synonymous_variant	10/14	ENST00000270066.11	NP_061981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG9	ENST00000270066.11	c.1062A>C	p.Ser354=	synonymous_variant	10/14	1	NM_019108.4	ENSP00000270066	P1
SMG9	ENST00000601170.5	c.1062A>C	p.Ser354=	synonymous_variant	10/13	2		ENSP00000471398
SMG9	ENST00000598860.1	n.397A>C		non_coding_transcript_exon_variant	1/3	2
SMG9	ENST00000597598.1			downstream_gene_variant		5		ENSP00000471442

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10 AN: 151710 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00732 AC: 10034 AN: 1371356 Hom.: 0 Cov.: 31 AF XY: 0.00693 AC XY: 4700 AN XY: 678590

Gnomad4 AFR exome AF: 0.00588

Gnomad4 AMR exome AF: 0.000326

Gnomad4 ASJ exome AF: 0.00281

Gnomad4 EAS exome AF: 0.00143

Gnomad4 SAS exome AF: 0.00275

Gnomad4 FIN exome AF: 0.000282

Gnomad4 NFE exome AF: 0.00870

Gnomad4 OTH exome AF: 0.00584

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000659 AC: 10 AN: 151832 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74224

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.0000737

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.049
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs996208121; hg19: chr19-44238581;