9-128322349-C-T

Variant names:

• chr9-128322349-C-T
• rs11539570
• NM_015679.3:c.60G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015679.3(TRUB2):​c.60G>A​(p.Gly20Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,614,170 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: TRUB2 NM_015679.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.334
• Publications: 8 publications found

Genes affected

TRUB2 (HGNC:17170): (TruB pseudouridine synthase family member 2) Pseudouridine is an abundant component of rRNAs and tRNAs and is enzymatically generated by isomerization of uridine by pseudouridine synthase (Zucchini et al., 2003 [PubMed 12736709]).[supplied by OMIM, Mar 2008]

COQ4 (HGNC:19693): (coenzyme Q4) This gene encodes a component of the coenzyme Q biosynthesis pathway. Coenzyme Q, an essential component of the electron transport chain, shuttles electrons between complexes I or II to complex III of the mitochondrial transport chain. This protein appears to play a structural role in stabilizing a complex that contains most of the coenzyme Q biosynthesis enzymes. Mutations in this gene are associated with mitochondrial disorders linked to coenzyme Q deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

COQ4 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 9-128322349-C-T is Benign according to our data. Variant chr9-128322349-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1194820.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.334 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRUB2	NM_015679.3	c.60G>A	p.Gly20Gly	synonymous_variant	Exon 1 of 8	ENST00000372890.6	NP_056494.1
TRUB2	NM_001329861.2	c.60G>A	p.Gly20Gly	synonymous_variant	Exon 1 of 7		NP_001316790.1
TRUB2	NM_001329863.2	c.-328G>A		5_prime_UTR_variant	Exon 1 of 9		NP_001316792.1
TRUB2	NM_001329862.2	c.-553G>A		upstream_gene_variant			NP_001316791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRUB2	ENST00000372890.6	c.60G>A	p.Gly20Gly	synonymous_variant	Exon 1 of 8	1	NM_015679.3	ENSP00000361982.4
TRUB2	ENST00000460320.1	n.65G>A		non_coding_transcript_exon_variant	Exon 1 of 9	2
COQ4	ENST00000608951.5	c.-510C>T		upstream_gene_variant		2		ENSP00000476323.1
COQ4	ENST00000609948.1	c.-510C>T		upstream_gene_variant		2		ENSP00000477292.1

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 349 AN: 152168 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00816

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000581 AC: 146 AN: 251458 AF XY: 0.000368

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000252 AC: 368 AN: 1461884 Hom.: 1 Cov.: 31 AF XY: 0.000204 AC XY: 148 AN XY: 727242

African (AFR) AF: 0.00968 AC: 324 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112008

Other (OTH) AF: 0.000513 AC: 31 AN: 60390

GnomAD4 genome AF: 0.00229 AC: 349 AN: 152286 Hom.: 2 Cov.: 33 AF XY: 0.00207 AC XY: 154 AN XY: 74452

African (AFR) AF: 0.00814 AC: 338 AN: 41548

American (AMR) AF: 0.000392 AC: 6 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00596 Hom.: 5

Bravo AF: 0.00274

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Uncertain	0.98
PhyloP100		-0.33
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11539570; hg19: chr9-131084628;