11-122656113-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032873.5(UBASH3B):c.64G>C(p.Val22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,600,994 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (13 hom.)
• Consequence: UBASH3B NM_032873.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.17

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005106777).
• BP6: Variant 11-122656113-G-C is Benign according to our data. Variant chr11-122656113-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 389 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBASH3B	NM_032873.5	c.64G>C	p.Val22Leu	missense_variant	1/14	ENST00000284273.6
UBASH3B	NM_001363365.2	c.-46G>C		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBASH3B	ENST00000284273.6	c.64G>C	p.Val22Leu	missense_variant	1/14	1	NM_032873.5	P1
UBASH3B	ENST00000525711.1	n.389G>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152176 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00428

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00241 AC: 532 AN: 220510 Hom.: 4 AF XY: 0.00246 AC XY: 297 AN XY: 120782

Gnomad AFR exome AF: 0.000471

Gnomad AMR exome AF: 0.000308

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000644

Gnomad FIN exome AF: 0.00431

Gnomad NFE exome AF: 0.00418

Gnomad OTH exome AF: 0.00185

GnomAD4 exome AF: 0.00305 AC: 4418 AN: 1448700 Hom.: 13 Cov.: 34 AF XY: 0.00302 AC XY: 2174 AN XY: 719884

Gnomad4 AFR exome AF: 0.000275

Gnomad4 AMR exome AF: 0.000343

Gnomad4 ASJ exome AF: 0.000155

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000856

Gnomad4 FIN exome AF: 0.00522

Gnomad4 NFE exome AF: 0.00355

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152294 Hom.: 1 Cov.: 31 AF XY: 0.00246 AC XY: 183 AN XY: 74474

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.00428

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00166 Hom.: 0

Bravo AF: 0.00195

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.000685 AC: 3

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00247 AC: 298

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

UBASH3B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	23
Dann	Benign	0.95
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	0.97	D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.030
Sift	Benign	0.14	T
Sift4G	Benign	0.60	T
Polyphen		0.54	P
Vest4		0.32
MVP		0.15
MPC		0.47
ClinPred		0.020	T
GERP RS		3.4
Varity_R		0.084
gMVP		0.38

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

Other links and lift over

dbSNP: rs150696870; hg19: chr11-122526821;