20-3147001-C-T

Variant names:

• chr20-3147001-C-T
• rs1331570689
• NM_021826.5:c.2070G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021826.5(FASTKD5):​c.2070G>A​(p.Met690Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FASTKD5 NM_021826.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0520
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053859174).

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.2070G>A	p.Met690Ile	missense	Exon 2 of 2	NP_068598.1	Q7L8L6
	UBOX5	NM_014948.4	MANE Select	c.-42+12765G>A		intron	N/A	NP_055763.1	O94941-1
	UBOX5	NM_001267584.2		c.-42+12765G>A		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.2070G>A	p.Met690Ile	missense	Exon 2 of 2	ENSP00000369618.3	Q7L8L6
	UBOX5	ENST00000217173.7	TSL:1 MANE Select	c.-42+12765G>A		intron	N/A	ENSP00000217173.2	O94941-1
	UBOX5	ENST00000348031.6	TSL:1	c.-42+12765G>A		intron	N/A	ENSP00000311726.3	O94941-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.5
DANN	Benign	0.54
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.052
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.025
Sift	Benign	0.43	T
Sift4G	Benign	0.50	T
Polyphen		0.0030	B
Vest4		0.062
MutPred		0.44		Loss of loop (P = 0.0112)
MVP		0.13
MPC		0.079
ClinPred		0.041	T
GERP RS		2.0
Varity_R		0.044
gMVP		0.11
Mutation Taster		=97/3	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: rs1331570689; hg19: chr20-3127647;