12-122206811-C-T

Variant names:

• chr12-122206811-C-T
• rs773738674
• NM_030765.4:c.560C>T

Variant summary

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

The NM_030765.4(B3GNT4):​c.560C>T​(p.Thr187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.9e-7 (0 hom.)
• Consequence: B3GNT4 NM_030765.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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=0.05007103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT4	NM_030765.4	c.560C>T	p.Thr187Ile	missense_variant	Exon 3 of 3	ENST00000324189.5	NP_110392.1
B3GNT4	NM_001330492.2	c.485C>T	p.Thr162Ile	missense_variant	Exon 2 of 2		NP_001317421.1
B3GNT4	XM_047429535.1	c.485C>T	p.Thr162Ile	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.560C>T	p.Thr187Ile	missense_variant	Exon 3 of 3	1	NM_030765.4	ENSP00000319636.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459784 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726126

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.14	T;.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.31	N;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.34	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.013	B;.;.
Vest4		0.060
MutPred		0.57		Loss of sheet (P = 0.1158);.;.;
MVP		0.23
MPC		0.012
ClinPred		0.089	T
GERP RS		0.67
Varity_R		0.069
gMVP		0.21

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: rs773738674; hg19: chr12-122691358;