chr2-231398213-G-C

Variant names:

• chr2-231398213-G-C
• rs774354408
• NM_145236.3:c.494G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145236.3(B3GNT7):​c.494G>C​(p.Gly165Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,446,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G165D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: B3GNT7 NM_145236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 0 publications found

Genes affected

B3GNT7 (HGNC:18811): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7) Predicted to enable UDP-glycosyltransferase activity. Predicted to be involved in poly-N-acetyllactosamine biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36437187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT7	NM_145236.3	MANE Select	c.494G>C	p.Gly165Ala	missense	Exon 2 of 2	NP_660279.1	Q8NFL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT7	ENST00000287590.6	TSL:1 MANE Select	c.494G>C	p.Gly165Ala	missense	Exon 2 of 2	ENSP00000287590.5	Q8NFL0
	B3GNT7	ENST00000714191.1		c.494G>C	p.Gly165Ala	missense	Exon 2 of 4	ENSP00000519481.1	A0AAQ5BHP6
	B3GNT7	ENST00000479618.1	TSL:4	n.583G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446960 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718552

African (AFR) AF: 0.00 AC: 0 AN: 33138

American (AMR) AF: 0.00 AC: 0 AN: 43410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.00 AC: 0 AN: 84516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104540

Other (OTH) AF: 0.00 AC: 0 AN: 59710

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.18
MutPred		0.57		Loss of catalytic residue at A164 (P = 0.0827)
MVP		0.15
MPC		1.4
ClinPred		0.93	D
GERP RS		3.4
Varity_R		0.18
gMVP		0.78
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs774354408; hg19: chr2-232262924;