chr13-31215075-CAAAG-C

Variant names:

• chr13-31215075-CAAAG-C
• rs759505367
• NM_194318.4:c.101_104delAAGA

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_194318.4(B3GLCT):​c.101_104delAAGA​(p.Lys34ArgfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: B3GLCT NM_194318.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.90

Genes affected

B3GLCT (HGNC:20207): (beta 3-glucosyltransferase) The protein encoded by this gene is a beta-1,3-glucosyltransferase that transfers glucose to O-linked fucosylglycans on thrombospondin type-1 repeats (TSRs) of several proteins. The encoded protein is a type II membrane protein. Defects in this gene are a cause of Peters-plus syndrome (PPS).[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-31215075-CAAAG-C is Pathogenic according to our data. Variant chr13-31215075-CAAAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 1324051.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GLCT	NM_194318.4	c.101_104delAAGA	p.Lys34ArgfsTer19	frameshift_variant	Exon 2 of 15	ENST00000343307.5	NP_919299.3
B3GLCT	XM_006719768.4	c.44_47delAAGA	p.Lys15ArgfsTer19	frameshift_variant	Exon 2 of 15		XP_006719831.1
B3GLCT	XM_011534936.2	c.101_104delAAGA	p.Lys34ArgfsTer19	frameshift_variant	Exon 2 of 14		XP_011533238.1
B3GLCT	XM_047430111.1	c.101_104delAAGA	p.Lys34ArgfsTer19	frameshift_variant	Exon 2 of 12		XP_047286067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5	c.101_104delAAGA	p.Lys34ArgfsTer19	frameshift_variant	Exon 2 of 15	1	NM_194318.4	ENSP00000343002.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000802 AC: 2 AN: 249374 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134838

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456810 Hom.: 0 AF XY: 0.00000276 AC XY: 2 AN XY: 724778

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.000111 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peters plus syndrome Pathogenic:1

Apr 03, 2020

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs759505367; hg19: chr13-31789212;