rs997345764

Variant names:

• chr1-235504210-C-A
• rs997345764
• NM_152490.5:c.43G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-235504210-C-A
• chr1-235504210-C-T

Variant summary

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

The NM_152490.5(B3GALNT2):​c.43G>T​(p.Ala15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000768 in 1,301,330 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. A15T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: B3GALNT2 NM_152490.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39909223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALNT2	NM_152490.5	c.43G>T	p.Ala15Ser	missense_variant	Exon 1 of 12	ENST00000366600.8	NP_689703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALNT2	ENST00000366600.8	c.43G>T	p.Ala15Ser	missense_variant	Exon 1 of 12	1	NM_152490.5	ENSP00000355559.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.68e-7 AC: 1 AN: 1301330 Hom.: 0 Cov.: 33 AF XY: 0.00000156 AC XY: 1 AN XY: 641508

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26120

American (AMR) AF: 0.00 AC: 0 AN: 23376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22286

East Asian (EAS) AF: 0.00 AC: 0 AN: 27398

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3898

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041374

Other (OTH) AF: 0.00 AC: 0 AN: 53724

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	0.90	L;L
PhyloP100		2.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.76	N;N
REVEL	Benign	0.054
Sift	Benign	0.071	T;.
Sift4G	Benign	0.097	T;T
Polyphen		0.50	P;D
Vest4		0.29
MutPred		0.25		Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);
MVP		0.65
MPC		0.37
ClinPred		0.78	D
GERP RS		4.3
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.53
Mutation Taster		=71/29	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: rs997345764; hg19: chr1-235667510;