chr11-122794721-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032873.5. 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
	UBASH3B	NM_032873.5	MANE Select	c.1000A>G	p.Thr334Ala	missense	Exon 7 of 14	NP_116262.2
	UBASH3B	NM_001363365.2		c.895A>G	p.Thr299Ala	missense	Exon 7 of 14	NP_001350294.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3B	ENST00000284273.6	TSL:1 MANE Select	c.1000A>G	p.Thr334Ala	missense	Exon 7 of 14	ENSP00000284273.5	Q8TF42
	UBASH3B	ENST00000526493.1	TSL:3	n.1088A>G		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000285909	ENST00000649590.1		n.74-28672T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	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
PhyloP100		2.1
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
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

hg19: chr11-122665429;