17-76265586-G-T

Variant names:

• chr17-76265586-G-T
• rs1437940507
• NM_182565.4:c.81G>T

Variant summary

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

The NM_182565.4(UBALD2):​c.81G>T​(p.Gln27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000841 in 1,189,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: UBALD2 NM_182565.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

Genes affected

UBALD2 (HGNC:28438): (UBA like domain containing 2)

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 rank	MANE	Protein	UniProt
UBALD2	NM_182565.4	c.81G>T	p.Gln27His	missense_variant	Exon 1 of 3	ENST00000327490.8	NP_872371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBALD2	ENST00000327490.8	c.81G>T	p.Gln27His	missense_variant	Exon 1 of 3	1	NM_182565.4	ENSP00000331298.6
UBALD2	ENST00000587913.1	c.-61+183G>T		intron_variant	Intron 1 of 2	3		ENSP00000468297.1
UBALD2	ENST00000589240.1	c.-381G>T		upstream_gene_variant		2		ENSP00000466518.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.41e-7 AC: 1 AN: 1189448 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 590222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000273

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.81G>T (p.Q27H) alteration is located in exon 1 (coding exon 1) of the UBALD2 gene. This alteration results from a G to T substitution at nucleotide position 81, causing the glutamine (Q) at amino acid position 27 to be replaced by a histidine (H). 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	0.93
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.86	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.55
MutPred		0.44		Loss of ubiquitination at K29 (P = 0.1139);
MVP		0.52
MPC		2.3
ClinPred		0.99	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.71
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1437940507; hg19: chr17-74261667;