chr5-159283323-C-T

Variant names:

• chr5-159283323-C-T
• NM_145049.5:c.913C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145049.5(UBLCP1):​c.913C>T​(p.His305Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBLCP1 NM_145049.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBLCP1	NM_145049.5	c.913C>T	p.His305Tyr	missense_variant	Exon 10 of 11	ENST00000296786.8	NP_659486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBLCP1	ENST00000296786.8	c.913C>T	p.His305Tyr	missense_variant	Exon 10 of 11	1	NM_145049.5	ENSP00000296786.6
UBLCP1	ENST00000519276.1	n.409C>T		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.913C>T (p.H305Y) alteration is located in exon 10 (coding exon 9) of the UBLCP1 gene. This alteration results from a C to T substitution at nucleotide position 913, causing the histidine (H) at amino acid position 305 to be replaced by a tyrosine (Y). 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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.75		Loss of helix (P = 0.0376);
MVP		0.67
MPC		1.7
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.91
gMVP		0.84
Mutation Taster		=51/49	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

Publications

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Other links and lift over

hg19: chr5-158710331; COSMIC: COSV99707420;