NM_194318.4:c.348T>C

Variant names:

• chr13-31247855-T-C
• rs4943266
• NM_194318.4:c.348T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_194318.4(B3GLCT):​c.348T>C​(p.His116His) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,541,690 control chromosomes in the GnomAD database, including 740,651 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71544 hom., cov: 32)
  • Exomes 𝑓: 0.98 (669107 hom.)
• Consequence: B3GLCT NM_194318.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0005678
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.312
• Publications: 21 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-31247855-T-C is Benign according to our data. Variant chr13-31247855-T-C is described in ClinVar as Benign. ClinVar VariationId is 96628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.312 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.348T>C	p.His116His	splice_region synonymous	Exon 6 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.348T>C	p.His116His	splice_region synonymous	Exon 6 of 15	ENSP00000343002.4	Q6Y288
	B3GLCT	ENST00000873566.1		c.271-13091T>C		intron	N/A	ENSP00000543625.1
	B3GLCT	ENST00000946543.1		c.121-13091T>C		intron	N/A	ENSP00000616602.1

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147477 AN: 152180 Hom.: 71508 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.974

GnomAD2 exomes AF: 0.984 AC: 245398 AN: 249382 AF XY: 0.985

Gnomad AFR exome AF: 0.927

Gnomad AMR exome AF: 0.990

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.982

Gnomad OTH exome AF: 0.987

GnomAD4 exome AF: 0.981 AC: 1363453 AN: 1389392 Hom.: 669107 Cov.: 21 AF XY: 0.982 AC XY: 683161 AN XY: 695672

African (AFR) AF: 0.926 AC: 29625 AN: 31994

American (AMR) AF: 0.989 AC: 44055 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 25417 AN: 25550

East Asian (EAS) AF: 1.00 AC: 39209 AN: 39210

South Asian (SAS) AF: 0.994 AC: 84075 AN: 84586

European-Finnish (FIN) AF: 0.992 AC: 52794 AN: 53210

Middle Eastern (MID) AF: 0.987 AC: 5422 AN: 5492

European-Non Finnish (NFE) AF: 0.980 AC: 1026107 AN: 1046938

Other (OTH) AF: 0.981 AC: 56749 AN: 57872

GnomAD4 genome AF: 0.969 AC: 147571 AN: 152298 Hom.: 71544 Cov.: 32 AF XY: 0.971 AC XY: 72283 AN XY: 74474

African (AFR) AF: 0.928 AC: 38568 AN: 41548

American (AMR) AF: 0.983 AC: 15038 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3446 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 0.994 AC: 4795 AN: 4822

European-Finnish (FIN) AF: 0.993 AC: 10545 AN: 10616

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66757 AN: 68040

Other (OTH) AF: 0.974 AC: 2061 AN: 2116

Alfa AF: 0.980 Hom.: 110440

Bravo AF: 0.966

Asia WGS AF: 0.991 AC: 3441 AN: 3472

EpiCase AF: 0.984

EpiControl AF: 0.983

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.47
PhyloP100		-0.31
Mutation Taster		=70/30	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00057
dbscSNV1_RF	Benign	0.060
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

Other links and lift over

dbSNP: rs4943266; hg19: chr13-31821992;