chr19-40700388-T-TGTC

Variant names:

• chr19-40700388-T-TGTC
• rs1057519346
• NM_024876.4:c.954_956dupGAC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_024876.4(COQ8B):​c.954_956dupGAC​(p.Thr319dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: COQ8B NM_024876.4 disruptive_inframe_insertion
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.289
• Publications: 2 publications found

Genes affected

COQ8B (HGNC:19041): (coenzyme Q8B) This gene encodes a protein with two copies of a domain found in protein kinases. The encoded protein has a complete protein kinase catalytic domain, and a truncated domain that contains only the active and binding sites of the protein kinase domain, however, it is not known whether the protein has any kinase activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

COQ8B Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• nephrotic syndrome, type 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_024876.4. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024876.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8B	NM_024876.4	MANE Select	c.954_956dupGAC	p.Thr319dup	disruptive_inframe_insertion	Exon 11 of 15	NP_079152.3
	COQ8B	NM_001142555.3		c.831_833dupGAC	p.Thr278dup	disruptive_inframe_insertion	Exon 10 of 14	NP_001136027.1	Q96D53-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8B	ENST00000324464.8	TSL:1 MANE Select	c.954_956dupGAC	p.Thr319dup	disruptive_inframe_insertion	Exon 11 of 15	ENSP00000315118.3	Q96D53-1
	COQ8B	ENST00000243583.10	TSL:1	c.831_833dupGAC	p.Thr278dup	disruptive_inframe_insertion	Exon 10 of 14	ENSP00000243583.5	Q96D53-2
	COQ8B	ENST00000871658.1		c.999_1001dupGAC	p.Thr334dup	disruptive_inframe_insertion	Exon 11 of 15	ENSP00000541717.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461818 Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

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: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Nephrotic syndrome, type 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29
Mutation Taster		=78/22	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1057519346; hg19: chr19-41206293;