20-3147426-C-T

Variant names:

• chr20-3147426-C-T
• NM_021826.5:c.1645G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021826.5(FASTKD5):​c.1645G>A​(p.Ala549Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FASTKD5 NM_021826.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1645G>A	p.Ala549Thr	missense	Exon 2 of 2	NP_068598.1	Q7L8L6
	UBOX5	NM_014948.4	MANE Select	c.-42+12340G>A		intron	N/A	NP_055763.1	O94941-1
	UBOX5	NM_001267584.2		c.-42+12340G>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.1645G>A	p.Ala549Thr	missense	Exon 2 of 2	ENSP00000369618.3	Q7L8L6
	UBOX5	ENST00000217173.7	TSL:1 MANE Select	c.-42+12340G>A		intron	N/A	ENSP00000217173.2	O94941-1
	UBOX5	ENST00000348031.6	TSL:1	c.-42+12340G>A		intron	N/A	ENSP00000311726.3	O94941-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

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	0.25
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.14
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.49		Gain of loop (P = 0.0312)
MVP		0.67
MPC		0.41
ClinPred		0.86	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.57
Mutation Taster		=81/19	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

hg19: chr20-3128072;