NM_014388.7:c.559C>A

Variant names:

• chr1-209833355-C-A
• rs575126483
• NM_014388.7:c.559C>A

Variant summary

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

The NM_014388.7(UTP25):​c.559C>A​(p.Gln187Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,415,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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. Q187E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UTP25 NM_014388.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

Genes affected

UTP25 (HGNC:28440): (UTP25 small subunit processome component) Enables RNA binding activity. Involved in several processes, including protein catabolic process; protein destabilization; and protein localization to nucleolus. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06254873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014388.7. 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
	UTP25	NM_014388.7	MANE Select	c.559C>A	p.Gln187Lys	missense	Exon 4 of 12	NP_055203.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP25	ENST00000491415.7	TSL:1 MANE Select	c.559C>A	p.Gln187Lys	missense	Exon 4 of 12	ENSP00000419005.1	Q68CQ4
	UTP25	ENST00000852870.1		c.550C>A	p.Gln184Lys	missense	Exon 4 of 12	ENSP00000522929.1
	UTP25	ENST00000915424.1		c.559C>A	p.Gln187Lys	missense	Exon 4 of 12	ENSP00000585483.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1415264 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 700854

African (AFR) AF: 0.00 AC: 0 AN: 31432

American (AMR) AF: 0.00 AC: 0 AN: 35848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22834

East Asian (EAS) AF: 0.0000510 AC: 2 AN: 39194

South Asian (SAS) AF: 0.00 AC: 0 AN: 77388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092730

Other (OTH) AF: 0.00 AC: 0 AN: 58392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.43
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.053
Sift	Benign	0.97	T
Sift4G	Benign	0.67	T
Vest4		0.070
MutPred		0.40		Gain of ubiquitination at Q187 (P = 0.0014)
MVP		0.33
MPC		0.15
ClinPred		0.041	T
GERP RS		3.7
gMVP		0.12
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs575126483; hg19: chr1-210006700;