1-20191103-A-T

Variant names:

• chr1-20191103-A-T
• NM_152376.5:c.542A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152376.5(UBXN10):​c.542A>T​(p.Gln181Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBXN10 NM_152376.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.150

Genes affected

UBXN10 (HGNC:26354): (UBX domain protein 10) Involved in cilium assembly. Located in cilium. Colocalizes with intraciliary transport particle B. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09095073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN10	NM_152376.5	c.542A>T	p.Gln181Leu	missense_variant	Exon 2 of 2	ENST00000375099.4	NP_689589.1
UBXN10	XM_005245742.5	c.542A>T	p.Gln181Leu	missense_variant	Exon 2 of 2		XP_005245799.1
UBXN10	XM_011540699.4	c.542A>T	p.Gln181Leu	missense_variant	Exon 2 of 2		XP_011539001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN10	ENST00000375099.4	c.542A>T	p.Gln181Leu	missense_variant	Exon 2 of 2	1	NM_152376.5	ENSP00000364240.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.542A>T (p.Q181L) alteration is located in exon 2 (coding exon 1) of the UBXN10 gene. This alteration results from a A to T substitution at nucleotide position 542, causing the glutamine (Q) at amino acid position 181 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.057
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.028	B
Vest4		0.15
MutPred		0.44		Loss of methylation at K179 (P = 0.0534);
MVP		0.040
MPC		0.38
ClinPred		0.28	T
GERP RS		0.92
Varity_R		0.18
gMVP		0.60

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: chr1-20517596;