11-122779487-T-C

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.403-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,613,518 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (24 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (14 hom.)
• Consequence: UBASH3B NM_032873.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001657
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.157

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 (BayesDel_noAF=-0.74).
• BP6: Variant 11-122779487-T-C is Benign according to our data. Variant chr11-122779487-T-C is described in ClinVar as [Benign]. Clinvar id is 781237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00838 (1276/152332) while in subpopulation AFR AF= 0.0294 (1222/41564). AF 95% confidence interval is 0.028. There are 24 homozygotes in gnomad4. There are 596 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1278 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBASH3B	NM_032873.5	c.403-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000284273.6
UBASH3B	NM_001363365.2	c.298-10T>C		splice_polypyrimidine_tract_variant, intron_variant
UBASH3B	XM_005271712.4	c.487-10T>C		splice_polypyrimidine_tract_variant, intron_variant
UBASH3B	XM_011543041.3	c.346-10T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBASH3B	ENST00000284273.6	c.403-10T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_032873.5	P1
	ENST00000649590.1	n.74-13438A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00840 AC: 1278 AN: 152214 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00228 AC: 570 AN: 249636 Hom.: 12 AF XY: 0.00169 AC XY: 228 AN XY: 135072

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.00121

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: 0.0000446

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000787 AC: 1150 AN: 1461186 Hom.: 14 Cov.: 33 AF XY: 0.000677 AC XY: 492 AN XY: 726916

Gnomad4 AFR exome AF: 0.0284

Gnomad4 AMR exome AF: 0.00145

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: 0.0000261

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00838 AC: 1276 AN: 152332 Hom.: 24 Cov.: 32 AF XY: 0.00800 AC XY: 596 AN XY: 74486

Gnomad4 AFR AF: 0.0294

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: 0.0000441

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00675 Hom.: 2

Bravo AF: 0.00974

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

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	8.8
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.020		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: rs200801128; hg19: chr11-122650195;