1-209833326-G-A

Position:

• chr1-209833326-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014388.7(UTP25):​c.530G>A​(p.Ser177Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,436,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: UTP25 NM_014388.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06611729).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTP25	NM_014388.7	c.530G>A	p.Ser177Asn	missense_variant	4/12	ENST00000491415.7	NP_055203.4
UTP25	XM_006711275.4	c.530G>A	p.Ser177Asn	missense_variant	4/10		XP_006711338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTP25	ENST00000491415.7	c.530G>A	p.Ser177Asn	missense_variant	4/12	1	NM_014388.7	ENSP00000419005.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1436518 Hom.: 0 Cov.: 33 AF XY: 0.00000421 AC XY: 3 AN XY: 713332

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000363

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.530G>A (p.S177N) alteration is located in exon 4 (coding exon 4) of the DIEXF gene. This alteration results from a G to A substitution at nucleotide position 530, causing the serine (S) at amino acid position 177 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.93
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.069
Sift	Benign	0.42	T
Sift4G	Benign	0.46	T
Vest4		0.037
MutPred		0.21		Loss of phosphorylation at S177 (P = 0.0118);
MVP		0.38
MPC		0.11
ClinPred		0.055	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.085

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-210006671; COSMIC: COSV105365929;