5-172212207-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152277.3(UBTD2):​c.328G>A​(p.Asp110Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,452,812 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: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UBTD2
NM_152277.3 missense

Scores

12
2
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70
Variant links:
Genes affected
UBTD2 (HGNC:24463): (ubiquitin domain containing 2) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBTD2NM_152277.3 linkc.328G>A p.Asp110Asn missense_variant Exon 3 of 3 ENST00000393792.3 NP_689490.2 Q8WUN7B3KMW8
UBTD2XM_017010022.2 linkc.196G>A p.Asp66Asn missense_variant Exon 3 of 3 XP_016865511.1 Q8WUN7B2R886
UBTD2XM_047417875.1 linkc.196G>A p.Asp66Asn missense_variant Exon 3 of 3 XP_047273831.1
UBTD2XM_047417876.1 linkc.196G>A p.Asp66Asn missense_variant Exon 4 of 4 XP_047273832.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBTD2ENST00000393792.3 linkc.328G>A p.Asp110Asn missense_variant Exon 3 of 3 1 NM_152277.3 ENSP00000377381.2 Q8WUN7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000804
AC:
2
AN:
248674
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134508
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1452812
Hom.:
0
Cov.:
30
AF XY:
0.00000416
AC XY:
3
AN XY:
720824
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000226
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.328G>A (p.D110N) alteration is located in exon 3 (coding exon 3) of the UBTD2 gene. This alteration results from a G to A substitution at nucleotide position 328, causing the aspartic acid (D) at amino acid position 110 to be replaced by an asparagine (N). 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
1.0
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.24
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.45
T
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
1.0
D
M_CAP
Benign
0.049
D
MetaRNN
Pathogenic
0.93
D
MetaSVM
Benign
-0.34
T
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-4.8
D
REVEL
Uncertain
0.51
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.95
MutPred
0.78
Gain of helix (P = 0.2294);
MVP
0.51
MPC
1.3
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.97
gMVP
0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs746821079; hg19: chr5-171639211; API