5-159278256-A-G

Position:

• chr5-159278256-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000296786.8(UBLCP1):​c.703A>G​(p.Ile235Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBLCP1 ENST00000296786.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07

Genes affected

UBLCP1 (HGNC:28110): (ubiquitin like domain containing CTD phosphatase 1) Enables protein serine/threonine phosphatase activity. Involved in protein dephosphorylation. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBLCP1	NM_145049.5	c.703A>G	p.Ile235Val	missense_variant	9/11	ENST00000296786.8	NP_659486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBLCP1	ENST00000296786.8	c.703A>G	p.Ile235Val	missense_variant	9/11	1	NM_145049.5	ENSP00000296786	P1
UBLCP1	ENST00000519276.1	n.199A>G		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jun 05, 2023

The c.703A>G (p.I235V) alteration is located in exon 9 (coding exon 8) of the UBLCP1 gene. This alteration results from a A to G substitution at nucleotide position 703, causing the isoleucine (I) at amino acid position 235 to be replaced by a valine (V). 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	0.24
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0075	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.98	N
REVEL	Uncertain	0.31
Sift	Benign	0.067	T
Sift4G	Benign	0.082	T
Polyphen		0.99	D
Vest4		0.24
MutPred		0.74		Gain of sheet (P = 0.0477);
MVP		0.55
MPC		0.98
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.14
gMVP		0.57

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-158705264;