rs147485868

Variant names:

• chr13-31323773-G-A
• rs147485868
• NM_194318.4:c.1207G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-31323773-G-A
• chr13-31323773-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_194318.4(B3GLCT):​c.1207G>A​(p.Val403Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,614,130 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: B3GLCT NM_194318.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:2
• Conservation: PhyloP100: 2.13
• Publications: 7 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), G2P, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017538518).
• BP6: Variant 13-31323773-G-A is Benign according to our data. Variant chr13-31323773-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 425025.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.1207G>A	p.Val403Ile	missense	Exon 14 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.1207G>A	p.Val403Ile	missense	Exon 14 of 15	ENSP00000343002.4	Q6Y288
	B3GLCT	ENST00000873566.1		c.1018G>A	p.Val340Ile	missense	Exon 12 of 13	ENSP00000543625.1
	B3GLCT	ENST00000946543.1		c.868G>A	p.Val290Ile	missense	Exon 10 of 11	ENSP00000616602.1

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00213

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00119 AC: 298 AN: 251458 AF XY: 0.00125

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00202

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00172 AC: 2509 AN: 1461856 Hom.: 4 Cov.: 31 AF XY: 0.00163 AC XY: 1184 AN XY: 727234

African (AFR) AF: 0.000329 AC: 11 AN: 33478

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86258

European-Finnish (FIN) AF: 0.00114 AC: 61 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.00209 AC: 2324 AN: 1111982

Other (OTH) AF: 0.00114 AC: 69 AN: 60396

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.00110 AC XY: 82 AN XY: 74464

African (AFR) AF: 0.000385 AC: 16 AN: 41558

American (AMR) AF: 0.000588 AC: 9 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.000755 AC: 8 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00213 AC: 145 AN: 68018

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00156 Hom.: 1

Bravo AF: 0.00107

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.00116 AC: 141

EpiCase AF: 0.00158

EpiControl AF: 0.00119

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	2	1	Peters plus syndrome (3)
-	-	1	B3GLCT-related disorder (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	12
DANN	Benign	0.73
DEOGEN2	Benign	0.057	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.32	N
REVEL	Uncertain	0.30
Sift	Benign	0.52	T
Sift4G	Benign	0.39	T
Polyphen		0.048	B
Vest4		0.24
MVP		0.33
MPC		0.20
ClinPred		0.015	T
GERP RS		-9.3
Varity_R		0.018
gMVP		0.30
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147485868; hg19: chr13-31897910; COSMIC: COSV58453697;