chr13-29772141-C-T

Variant names:

• chr13-29772141-C-T
• rs376057091
• NM_007106.4:c.194G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007106.4(UBL3):​c.194G>A​(p.Arg65Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,459,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: UBL3 NM_007106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31
• Publications: 1 publications found

Genes affected

UBL3 (HGNC:12504): (ubiquitin like 3) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.878

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007106.4. 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
	UBL3	NM_007106.4	MANE Select	c.194G>A	p.Arg65Gln	missense	Exon 3 of 5	NP_009037.1	O95164

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBL3	ENST00000380680.5	TSL:1 MANE Select	c.194G>A	p.Arg65Gln	missense	Exon 3 of 5	ENSP00000370055.4	O95164

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250078 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1459574 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 726038

African (AFR) AF: 0.0000300 AC: 1 AN: 33384

American (AMR) AF: 0.0000224 AC: 1 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 86032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110632

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

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	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MVP		0.54
MPC		1.7
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.51
gMVP		0.87
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs376057091; hg19: chr13-30346278; COSMIC: COSV101041616;