20-3147010-TGC-GCT

Variant names:

• chr20-3147010-TGC-GCT
• NM_021826.5:c.2059_2061delGCAinsAGC
• FASTKD5 p.Ala687Ser

Variant summary

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

The NM_021826.5(FASTKD5):​c.2059_2061delGCAinsAGC​(p.Ala687Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A687T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FASTKD5 NM_021826.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 0 publications found

Genes affected

FASTKD5 (HGNC:25790): (FAST kinase domains 5) Enables rRNA binding activity. Involved in mitochondrial RNA processing. Located in mitochondrial nucleoid and ribonucleoprotein granule. [provided by Alliance of Genome Resources, Apr 2022]

UBOX5 (HGNC:17777): (U-box domain containing 5) This gene encodes a U-box domain containing protein. The encoded protein interacts with E2 enzymes and may play a role in the ubiquitination pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

UBOX5-AS1 (HGNC:44111): (UBOX5 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021826.5. 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
	FASTKD5	NM_021826.5	MANE Select	c.2059_2061delGCAinsAGC	p.Ala687Ser	missense	N/A	NP_068598.1	Q7L8L6
	UBOX5	NM_014948.4	MANE Select	c.-42+12754_-42+12756delGCAinsAGC		intron	N/A	NP_055763.1	O94941-1
	UBOX5	NM_001267584.2		c.-42+12754_-42+12756delGCAinsAGC		intron	N/A	NP_001254513.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASTKD5	ENST00000380266.4	TSL:1 MANE Select	c.2059_2061delGCAinsAGC	p.Ala687Ser	missense	N/A	ENSP00000369618.3	Q7L8L6
	UBOX5	ENST00000217173.7	TSL:1 MANE Select	c.-42+12754_-42+12756delGCAinsAGC		intron	N/A	ENSP00000217173.2	O94941-1
	UBOX5	ENST00000348031.6	TSL:1	c.-42+12754_-42+12756delGCAinsAGC		intron	N/A	ENSP00000311726.3	O94941-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.035

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-3127656;