11-122794721-A-G

Variant names:

• chr11-122794721-A-G
• NM_032873.5:c.1000A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032873.5(UBASH3B):​c.1000A>G​(p.Thr334Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. T334I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBASH3B NM_032873.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07

Genes affected

UBASH3B (HGNC:29884): (ubiquitin associated and SH3 domain containing B) This gene encodes a protein that contains a ubiquitin associated domain at the N-terminus, an SH3 domain, and a C-terminal domain with similarities to the catalytic motif of phosphoglycerate mutase. The encoded protein was found to inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor. [provided by RefSeq, Jul 2008]

ENSG00000285909 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0571945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBASH3B	NM_032873.5	c.1000A>G	p.Thr334Ala	missense_variant	Exon 7 of 14	ENST00000284273.6	NP_116262.2
UBASH3B	NM_001363365.2	c.895A>G	p.Thr299Ala	missense_variant	Exon 7 of 14		NP_001350294.1
UBASH3B	XM_005271712.4	c.1084A>G	p.Thr362Ala	missense_variant	Exon 7 of 14		XP_005271769.1
UBASH3B	XM_011543041.3	c.943A>G	p.Thr315Ala	missense_variant	Exon 7 of 14		XP_011541343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBASH3B	ENST00000284273.6	c.1000A>G	p.Thr334Ala	missense_variant	Exon 7 of 14	1	NM_032873.5	ENSP00000284273.5
UBASH3B	ENST00000526493.1	n.1088A>G		non_coding_transcript_exon_variant	Exon 3 of 3	3
ENSG00000285909	ENST00000649590.1	n.74-28672T>C		intron_variant	Intron 1 of 6
UBASH3B	ENST00000530578.1	n.-57A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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.1000A>G (p.T334A) alteration is located in exon 7 (coding exon 7) of the UBASH3B gene. This alteration results from a A to G substitution at nucleotide position 1000, causing the threonine (T) at amino acid position 334 to be replaced by an alanine (A). 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	Benign	0.058
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.21
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.14
Sift	Benign	0.88	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.15		Loss of glycosylation at T334 (P = 0.1322);
MVP		0.23
MPC		0.47
ClinPred		0.11	T
GERP RS		5.4
Varity_R		0.057
gMVP		0.25

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: chr11-122665429;