12-122206597-A-C

Variant names:

• chr12-122206597-A-C
• rs144184548
• NM_030765.4:c.346A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030765.4(B3GNT4):​c.346A>C​(p.Lys116Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: B3GNT4 NM_030765.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045102775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT4	NM_030765.4	c.346A>C	p.Lys116Gln	missense_variant	Exon 3 of 3	ENST00000324189.5	NP_110392.1
B3GNT4	NM_001330492.2	c.271A>C	p.Lys91Gln	missense_variant	Exon 2 of 2		NP_001317421.1
B3GNT4	XM_047429535.1	c.271A>C	p.Lys91Gln	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.346A>C	p.Lys116Gln	missense_variant	Exon 3 of 3	1	NM_030765.4	ENSP00000319636.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251478 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135916

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.9
DANN	Benign	0.73
DEOGEN2	Benign	0.021	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.19	T;.;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.52	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.067
MutPred		0.34		Loss of methylation at K116 (P = 0.0182);.;.;
MVP		0.21
MPC		0.011
ClinPred		0.044	T
GERP RS		-10
Varity_R		0.072
gMVP		0.41

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: rs144184548; hg19: chr12-122691144;