11-122796180-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032873.5(UBASH3B):c.1138G>A(p.Gly380Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,048 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (7 hom.)
• Consequence: UBASH3B NM_032873.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002783209).
• BP6: Variant 11-122796180-G-A is Benign according to our data. Variant chr11-122796180-G-A is described in ClinVar as [Benign]. Clinvar id is 711917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00633 (964/152222) while in subpopulation AFR AF= 0.0218 (907/41542). AF 95% confidence interval is 0.0207. There are 13 homozygotes in gnomad4. There are 463 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 962 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBASH3B	NM_032873.5	c.1138G>A	p.Gly380Ser	missense_variant	8/14	ENST00000284273.6
UBASH3B	NM_001363365.2	c.1033G>A	p.Gly345Ser	missense_variant	8/14
UBASH3B	XM_005271712.4	c.1222G>A	p.Gly408Ser	missense_variant	8/14
UBASH3B	XM_011543041.3	c.1081G>A	p.Gly361Ser	missense_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBASH3B	ENST00000284273.6	c.1138G>A	p.Gly380Ser	missense_variant	8/14	1	NM_032873.5	P1
	ENST00000649590.1	n.74-30131C>T		intron_variant, non_coding_transcript_variant
UBASH3B	ENST00000530578.1	n.82G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.00632 AC: 962 AN: 152104 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00150 AC: 376 AN: 251330 Hom.: 3 AF XY: 0.00107 AC XY: 146 AN XY: 135828

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000650 AC: 950 AN: 1461826 Hom.: 7 Cov.: 31 AF XY: 0.000535 AC XY: 389 AN XY: 727216

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.00633 AC: 964 AN: 152222 Hom.: 13 Cov.: 32 AF XY: 0.00622 AC XY: 463 AN XY: 74422

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00116 Hom.: 5

Bravo AF: 0.00713

ESP6500AA AF: 0.0182 AC: 80

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00202 AC: 245

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	18
Dann	Benign	0.96
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.061
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.71	N
MutationTaster	Benign	0.95	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.028
Sift	Benign	0.88	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.29
MVP		0.068
MPC		0.48
ClinPred		0.018	T
GERP RS		4.6
Varity_R		0.050
gMVP		0.15

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: rs74578417; hg19: chr11-122666888;