rs1041073

Variant names:

• chr13-31317609-G-A
• rs1041073
• NM_194318.4:c.1108G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_194318.4(B3GLCT):​c.1108G>A​(p.Glu370Lys) variant causes a missense change. The variant allele was found at a frequency of 0.748 in 1,613,678 control chromosomes in the GnomAD database, including 456,734 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (36183 hom., cov: 31)
  • Exomes 𝑓: 0.76 (420551 hom.)
• Consequence: B3GLCT NM_194318.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 6.17
• Publications: 53 publications found

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]

B3GLCT Gene-Disease associations (from GenCC):

• Peters plus syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.169308E-6).
• BP6: Variant 13-31317609-G-A is Benign according to our data. Variant chr13-31317609-G-A is described in ClinVar as Benign. ClinVar VariationId is 96624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194318.4. 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
	B3GLCT	NM_194318.4	MANE Select	c.1108G>A	p.Glu370Lys	missense	Exon 13 of 15	NP_919299.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GLCT	ENST00000343307.5	TSL:1 MANE Select	c.1108G>A	p.Glu370Lys	missense	Exon 13 of 15	ENSP00000343002.4
	B3GLCT	ENST00000873566.1		c.919G>A	p.Glu307Lys	missense	Exon 11 of 13	ENSP00000543625.1
	B3GLCT	ENST00000946543.1		c.769G>A	p.Glu257Lys	missense	Exon 9 of 11	ENSP00000616602.1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101919 AN: 151882 Hom.: 36180 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.707

GnomAD2 exomes AF: 0.749 AC: 188293 AN: 251428 AF XY: 0.756

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.792

Gnomad ASJ exome AF: 0.837

Gnomad EAS exome AF: 0.786

Gnomad FIN exome AF: 0.714

Gnomad NFE exome AF: 0.774

Gnomad OTH exome AF: 0.761

GnomAD4 exome AF: 0.756 AC: 1105023 AN: 1461678 Hom.: 420551 Cov.: 50 AF XY: 0.758 AC XY: 551507 AN XY: 727158

African (AFR) AF: 0.401 AC: 13439 AN: 33474

American (AMR) AF: 0.787 AC: 35205 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 21894 AN: 26132

East Asian (EAS) AF: 0.758 AC: 30081 AN: 39694

South Asian (SAS) AF: 0.762 AC: 65684 AN: 86254

European-Finnish (FIN) AF: 0.710 AC: 37937 AN: 53398

Middle Eastern (MID) AF: 0.742 AC: 4281 AN: 5768

European-Non Finnish (NFE) AF: 0.766 AC: 851542 AN: 1111852

Other (OTH) AF: 0.745 AC: 44960 AN: 60384

GnomAD4 genome AF: 0.671 AC: 101952 AN: 152000 Hom.: 36183 Cov.: 31 AF XY: 0.673 AC XY: 49994 AN XY: 74294

African (AFR) AF: 0.417 AC: 17285 AN: 41426

American (AMR) AF: 0.752 AC: 11504 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2883 AN: 3472

East Asian (EAS) AF: 0.779 AC: 4010 AN: 5148

South Asian (SAS) AF: 0.767 AC: 3685 AN: 4802

European-Finnish (FIN) AF: 0.710 AC: 7499 AN: 10560

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52567 AN: 67994

Other (OTH) AF: 0.708 AC: 1489 AN: 2104

Alfa AF: 0.736 Hom.: 113497

Bravo AF: 0.663

TwinsUK AF: 0.767 AC: 2843

ALSPAC AF: 0.773 AC: 2978

ESP6500AA AF: 0.416 AC: 1833

ESP6500EA AF: 0.778 AC: 6691

ExAC AF: 0.742 AC: 90132

Asia WGS AF: 0.782 AC: 2718 AN: 3478

EpiCase AF: 0.774

EpiControl AF: 0.781

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Peters plus syndrome (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.035
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0000022	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.29
Sift	Benign	0.13	T
Sift4G	Benign	0.29	T
Polyphen		0.96	D
Vest4		0.26
MPC		0.34
ClinPred		0.034	T
GERP RS		3.2
Varity_R		0.098
gMVP		0.82
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

dbSNP: rs1041073; hg19: chr13-31891746; COSMIC: COSV108182900; COSMIC: COSV108182900;