chr1-20191208-G-C

Variant names:

• chr1-20191208-G-C
• NM_152376.5:c.647G>C

Variant summary

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

The NM_152376.5(UBXN10):​c.647G>C​(p.Arg216Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R216Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UBXN10 NM_152376.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN10	NM_152376.5	c.647G>C	p.Arg216Pro	missense_variant	Exon 2 of 2	ENST00000375099.4	NP_689589.1
UBXN10	XM_005245742.5	c.647G>C	p.Arg216Pro	missense_variant	Exon 2 of 2		XP_005245799.1
UBXN10	XM_011540699.4	c.647G>C	p.Arg216Pro	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.647G>C	p.Arg216Pro	missense_variant	Exon 2 of 2	1	NM_152376.5	ENSP00000364240.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.49		Loss of MoRF binding (P = 0.0032);
MVP		0.12
MPC		0.73
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.72
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-20517701;