17-82946930-C-G

Position:

• chr17-82946930-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000320865.4(B3GNTL1):​c.1014G>C​(p.Glu338Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,417,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: B3GNTL1 ENST00000320865.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0300

Genes affected

B3GNTL1 (HGNC:21727): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase like 1) Predicted to enable glycosyltransferase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26170254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GNTL1	NM_001009905.3	c.1014G>C	p.Glu338Asp	missense_variant	12/13	ENST00000320865.4	NP_001009905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GNTL1	ENST00000320865.4	c.1014G>C	p.Glu338Asp	missense_variant	12/13	1	NM_001009905.3	ENSP00000319979	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1417254 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 700612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000533

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2023

The c.1059G>C (p.E353D) alteration is located in exon 12 (coding exon 12) of the B3GNTL1 gene. This alteration results from a G to C substitution at nucleotide position 1059, causing the glutamic acid (E) at amino acid position 353 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Benign	0.28
Sift	Benign	0.057	.;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.98	.;D
Vest4		0.50
MutPred		0.31		.;Loss of catalytic residue at E353 (P = 0.031);
MVP		0.81
MPC		0.43
ClinPred		0.97	D
GERP RS		2.0
Varity_R		0.33
gMVP		0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80904806;