6-70861674-T-G

Position:

• chr6-70861674-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080742.3(B3GAT2):​c.961A>C​(p.Ile321Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GAT2 NM_080742.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

Genes affected

B3GAT2 (HGNC:922): (beta-1,3-glucuronyltransferase 2) The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes the transfer of a beta-1,3 linked glucuronic acid to a terminal galactose in different glycoproteins or glycolipids containing a Gal-beta-1-4GlcNAc or Gal-beta-1-3GlcNAc residue. The encoded protein is involved in the synthesis of the human natural killer-1 (HNK-1) carbohydrate epitope, a sulfated trisaccharide implicated in cellular migration and adhesion in the nervous system. [provided by RefSeq, Jul 2008]

SMAP1 (HGNC:19651): (small ArfGAP 1) The protein encoded by this gene is similar to the mouse stromal membrane-associated protein-1. This similarity suggests that this human gene product is also a type II membrane glycoprotein involved in the erythropoietic stimulatory activity of stromal cells. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38952297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GAT2	NM_080742.3	c.961A>C	p.Ile321Leu	missense_variant	4/4	ENST00000230053.11	NP_542780.1
SMAP1	NM_001044305.3	c.*1340T>G		3_prime_UTR_variant	11/11	ENST00000370455.8	NP_001037770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GAT2	ENST00000230053.11	c.961A>C	p.Ile321Leu	missense_variant	4/4	1	NM_080742.3	ENSP00000230053.6
B3GAT2	ENST00000615536.1	c.745A>C	p.Ile249Leu	missense_variant	4/4	1		ENSP00000481320.1
SMAP1	ENST00000370455.8	c.*1340T>G		3_prime_UTR_variant	11/11	1	NM_001044305.3	ENSP00000359484.3
SMAP1	ENST00000619054.4	c.*1340T>G		3_prime_UTR_variant	11/11	1		ENSP00000484538.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 04, 2024

The c.961A>C (p.I321L) alteration is located in exon 4 (coding exon 4) of the B3GAT2 gene. This alteration results from a A to C substitution at nucleotide position 961, causing the isoleucine (I) at amino acid position 321 to be replaced by a leucine (L). 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	Uncertain	0.46
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	0.068
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.16
Sift	Uncertain	0.0090	D;.
Sift4G	Uncertain	0.024	D;T
Polyphen		0.023	B;.
Vest4		0.56
MutPred		0.27		Loss of sheet (P = 0.0315);.;
MVP		0.32
MPC		0.62
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.68
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-71571377;