12-122206487-A-C

Variant names:

• chr12-122206487-A-C
• rs1370849165
• NM_030765.4:c.236A>C

Variant summary

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

The NM_030765.4(B3GNT4):​c.236A>C​(p.Asn79Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: B3GNT4 NM_030765.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22666341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT4	NM_030765.4	c.236A>C	p.Asn79Thr	missense_variant	Exon 3 of 3	ENST00000324189.5	NP_110392.1
B3GNT4	NM_001330492.2	c.161A>C	p.Asn54Thr	missense_variant	Exon 2 of 2		NP_001317421.1
B3GNT4	XM_047429535.1	c.161A>C	p.Asn54Thr	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.236A>C	p.Asn79Thr	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: 1461868 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000387 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.48	T;.;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.099
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.96	P;.;.
Vest4		0.42
MutPred		0.23		Gain of glycosylation at N79 (P = 0.0019);.;.;
MVP		0.53
MPC		0.061
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.21
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs1370849165; hg19: chr12-122691034;