1-20190662-T-G

Variant names:

• chr1-20190662-T-G
• rs2018477138
• NM_152376.5:c.101T>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_152376.5(UBXN10):​c.101T>G​(p.Met34Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. M34T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBXN10 NM_152376.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.30

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN10	NM_152376.5	c.101T>G	p.Met34Arg	missense_variant	Exon 2 of 2	ENST00000375099.4	NP_689589.1
UBXN10	XM_005245742.5	c.101T>G	p.Met34Arg	missense_variant	Exon 2 of 2		XP_005245799.1
UBXN10	XM_011540699.4	c.101T>G	p.Met34Arg	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.101T>G	p.Met34Arg	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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.77		Loss of sheet (P = 0.0084);
MVP		0.067
MPC		0.22
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.95
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs2018477138; hg19: chr1-20517155;