rs1553356108

Variant names:

• chr1-235504146-G-C
• rs1553356108
• NM_152490.5:c.107C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152490.5(B3GALNT2):​c.107C>G​(p.Pro36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,269,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: B3GALNT2 NM_152490.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

B3GALNT2 (HGNC:28596): (beta-1,3-N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2013]

B3GALNT2 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscle-eye-brain disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1364733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152490.5. 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
	B3GALNT2	NM_152490.5	MANE Select	c.107C>G	p.Pro36Arg	missense	Exon 1 of 12	NP_689703.1	Q8NCR0-1
	B3GALNT2	NM_001277155.3		c.107C>G	p.Pro36Arg	missense	Exon 1 of 8	NP_001264084.1	Q8NCR0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	ENST00000366600.8	TSL:1 MANE Select	c.107C>G	p.Pro36Arg	missense	Exon 1 of 12	ENSP00000355559.3	Q8NCR0-1
	B3GALNT2	ENST00000313984.3	TSL:1	c.107C>G	p.Pro36Arg	missense	Exon 1 of 8	ENSP00000315678.3	Q8NCR0-2
	B3GALNT2	ENST00000954792.1		c.107C>G	p.Pro36Arg	missense	Exon 1 of 13	ENSP00000624851.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151648 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000537 AC: 6 AN: 1118170 Hom.: 0 Cov.: 34 AF XY: 0.00000928 AC XY: 5 AN XY: 538834

African (AFR) AF: 0.00 AC: 0 AN: 22428

American (AMR) AF: 0.00 AC: 0 AN: 8044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14108

East Asian (EAS) AF: 0.00 AC: 0 AN: 25458

South Asian (SAS) AF: 0.000179 AC: 6 AN: 33598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2932

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 944420

Other (OTH) AF: 0.00 AC: 0 AN: 44254

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151758 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74196

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67844

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.52
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.47	N
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.054
Sift	Benign	0.41	T
Sift4G	Uncertain	0.016	D
Polyphen		0.019	B
Vest4		0.048
MutPred		0.29		Gain of methylation at P36 (P = 0.0162)
MVP		0.41
MPC		0.26
ClinPred		0.055	T
GERP RS		2.8
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.10
gMVP		0.52
Mutation Taster		=87/13	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: rs1553356108; hg19: chr1-235667446;