1-20190704-C-G

Variant names:

• chr1-20190704-C-G
• rs200664821
• NM_152376.5:c.143C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152376.5(UBXN10):​c.143C>G​(p.Pro48Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. P48L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: UBXN10 NM_152376.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32877034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN10	NM_152376.5	c.143C>G	p.Pro48Arg	missense_variant	Exon 2 of 2	ENST00000375099.4	NP_689589.1
UBXN10	XM_005245742.5	c.143C>G	p.Pro48Arg	missense_variant	Exon 2 of 2		XP_005245799.1
UBXN10	XM_011540699.4	c.143C>G	p.Pro48Arg	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.143C>G	p.Pro48Arg	missense_variant	Exon 2 of 2	1	NM_152376.5	ENSP00000364240.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250114 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135352

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727240

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.33
MutPred		0.35		Gain of solvent accessibility (P = 0.0026);
MVP		0.10
MPC		0.60
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.32
gMVP		0.34

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: rs200664821; hg19: chr1-20517197;