17-76265611-C-T

Variant names:

• chr17-76265611-C-T
• NM_182565.4:c.106C>T

Variant summary

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

The NM_182565.4(UBALD2):​c.106C>T​(p.His36Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBALD2 NM_182565.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49

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.106C>T	p.His36Tyr	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.106C>T	p.His36Tyr	missense_variant	Exon 1 of 3	1	NM_182565.4	ENSP00000331298.6
UBALD2	ENST00000587913.1	c.-61+208C>T		intron_variant	Intron 1 of 2	3		ENSP00000468297.1
UBALD2	ENST00000589240.1	c.-356C>T		upstream_gene_variant		2		ENSP00000466518.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1148806 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 567322

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: 0.00

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

Nov 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106C>T (p.H36Y) alteration is located in exon 1 (coding exon 1) of the UBALD2 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the histidine (H) at amino acid position 36 to be replaced by a tyrosine (Y). 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	0.76
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.015	D
Polyphen		0.78	P
Vest4		0.53
MutPred		0.51		Loss of disorder (P = 0.2692);
MVP		0.29
MPC		2.0
ClinPred		0.99	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-74261692;