10-97567916-C-G

Variant names:

• chr10-97567916-C-G
• rs144753553
• NM_024954.5:c.73C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024954.5(UBTD1):​c.73C>G​(p.Arg25Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. R25H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBTD1 NM_024954.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10
• Publications: 4 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024954.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTD1	NM_024954.5	MANE Select	c.73C>G	p.Arg25Gly	missense splice_region	Exon 2 of 3	NP_079230.1	Q9HAC8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTD1	ENST00000370664.4	TSL:1 MANE Select	c.73C>G	p.Arg25Gly	missense splice_region	Exon 2 of 3	ENSP00000359698.3	Q9HAC8
	UBTD1	ENST00000958439.1		c.166C>G	p.Arg56Gly	missense splice_region	Exon 3 of 4	ENSP00000628498.1
	UBTD1	ENST00000923989.1		c.71-2222C>G		intron	N/A	ENSP00000594048.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.29
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.074	T
Polyphen		1.0	D
Vest4		0.81
MutPred		0.15		Loss of MoRF binding (P = 0.0845)
MVP		0.34
MPC		1.2
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.58
gMVP		0.83
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs144753553; hg19: chr10-99327673;