rs144753553

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-97567916-C-T
• chr10-97567916-C-G

Variant summary

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

The NM_024954.5(UBTD1):​c.73C>T​(p.Arg25Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000374 in 1,614,048 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.00054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: UBTD1 NM_024954.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

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>T	p.Arg25Cys	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>T	p.Arg25Cys	missense splice_region	Exon 2 of 3	ENSP00000359698.3	Q9HAC8
	UBTD1	ENST00000958439.1		c.166C>T	p.Arg56Cys	missense splice_region	Exon 3 of 4	ENSP00000628498.1
	UBTD1	ENST00000923989.1		c.71-2222C>T		intron	N/A	ENSP00000594048.1

Frequencies

GnomAD3 genomes AF: 0.000539 AC: 82 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000395 AC: 99 AN: 250394 AF XY: 0.000458

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000509

Gnomad NFE exome AF: 0.000674

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000356 AC: 521 AN: 1461804 Hom.: 1 Cov.: 32 AF XY: 0.000388 AC XY: 282 AN XY: 727216

African (AFR) AF: 0.000119 AC: 4 AN: 33474

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86256

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000422 AC: 469 AN: 1111998

Other (OTH) AF: 0.000132 AC: 8 AN: 60396

GnomAD4 genome AF: 0.000539 AC: 82 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.000551 AC XY: 41 AN XY: 74420

African (AFR) AF: 0.0000722 AC: 3 AN: 41546

American (AMR) AF: 0.000915 AC: 14 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000559 Hom.: 0

Bravo AF: 0.000382

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000354 AC: 43

EpiCase AF: 0.000763

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.82
MVP		0.33
MPC		1.3
ClinPred		0.30	T
GERP RS		5.7
Varity_R		0.58
gMVP		0.81
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs144753553; hg19: chr10-99327673; COSMIC: COSV105881908; COSMIC: COSV105881908;