chr12-122206848-C-G

Variant names:

• chr12-122206848-C-G
• NM_030765.4:c.597C>G

Variant summary

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

The NM_030765.4(B3GNT4):​c.597C>G​(p.His199Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: B3GNT4 NM_030765.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0840

Genes affected

B3GNT4 (HGNC:15683): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase protein family. The encoded enzyme is involved in the biosynthesis of poly-N-acetyllactosamine chains and prefers lacto-N-neotetraose as a substrate. It is a type II transmembrane protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT4	NM_030765.4	c.597C>G	p.His199Gln	missense_variant	Exon 3 of 3	ENST00000324189.5	NP_110392.1
B3GNT4	NM_001330492.2	c.522C>G	p.His174Gln	missense_variant	Exon 2 of 2		NP_001317421.1
B3GNT4	XM_047429535.1	c.522C>G	p.His174Gln	missense_variant	Exon 2 of 2		XP_047285491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GNT4	ENST00000324189.5	c.597C>G	p.His199Gln	missense_variant	Exon 3 of 3	1	NM_030765.4	ENSP00000319636.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461450 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727042

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.597C>G (p.H199Q) alteration is located in exon 3 (coding exon 2) of the B3GNT4 gene. This alteration results from a C to G substitution at nucleotide position 597, causing the histidine (H) at amino acid position 199 to be replaced by a glutamine (Q). 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	0.50
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.78	T;.;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.50	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-7.0	D;D;D
REVEL	Benign	0.23
Sift	Benign	0.033	D;D;D
Sift4G	Uncertain	0.043	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.34
MutPred		0.64		Loss of catalytic residue at L198 (P = 0.227);.;.;
MVP		0.62
MPC		0.039
ClinPred		0.98	D
GERP RS		2.3
Varity_R		0.67
gMVP		0.63

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: chr12-122691395;