10-97567976-G-C

Position:

• chr10-97567976-G-C

Variant summary

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

The NM_024954.5(UBTD1):​c.133G>C​(p.Gly45Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBTD1 NM_024954.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.99

Genes affected

UBTD1 (HGNC:25683): (ubiquitin domain containing 1) The degradation of many proteins is carried out by the ubiquitin pathway in which proteins are targeted for degradation by covalent conjugation of the polypeptide ubiquitin. This gene encodes a protein that belongs to the ubiquitin family of proteins. The encoded protein is thought to regulate E2 ubiquitin conjugating enzymes belonging to the UBE2D family. [provided by RefSeq, Mar 2014]

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/exons	MANE	Protein	UniProt
UBTD1	NM_024954.5	c.133G>C	p.Gly45Arg	missense_variant	2/3	ENST00000370664.4	NP_079230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBTD1	ENST00000370664.4	c.133G>C	p.Gly45Arg	missense_variant	2/3	1	NM_024954.5	ENSP00000359698.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.133G>C (p.G45R) alteration is located in exon 2 (coding exon 2) of the UBTD1 gene. This alteration results from a G to C substitution at nucleotide position 133, causing the glycine (G) at amino acid position 45 to be replaced by an arginine (R). 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	0.97
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.36		Gain of solvent accessibility (P = 6e-04);
MVP		0.41
MPC		1.2
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.88
gMVP		0.92

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: chr10-99327733;