rs766891631

Variant names:

• chr1-235504172-C-A
• rs766891631
• NM_152490.5:c.81G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-235504172-C-A
• chr1-235504172-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_152490.5(B3GALNT2):​c.81G>T​(p.Pro27Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,297,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P27P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: B3GALNT2 NM_152490.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.59
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-235504172-C-A is Benign according to our data. Variant chr1-235504172-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 385271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	NM_152490.5	MANE Select	c.81G>T	p.Pro27Pro	synonymous	Exon 1 of 12	NP_689703.1
	B3GALNT2	NM_001277155.3		c.81G>T	p.Pro27Pro	synonymous	Exon 1 of 8	NP_001264084.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALNT2	ENST00000366600.8	TSL:1 MANE Select	c.81G>T	p.Pro27Pro	synonymous	Exon 1 of 12	ENSP00000355559.3
	B3GALNT2	ENST00000313984.3	TSL:1	c.81G>T	p.Pro27Pro	synonymous	Exon 1 of 8	ENSP00000315678.3
	B3GALNT2	ENST00000676288.1		c.81G>T	p.Pro27Pro	synonymous	Exon 1 of 13	ENSP00000502392.1

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 151770 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000951

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000457

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000794 AC: 3 AN: 3778 AF XY: 0.000906

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.00610

GnomAD4 exome AF: 0.000235 AC: 269 AN: 1145822 Hom.: 0 Cov.: 33 AF XY: 0.000220 AC XY: 122 AN XY: 554556

African (AFR) AF: 0.00 AC: 0 AN: 23228

American (AMR) AF: 0.00 AC: 0 AN: 9248

Ashkenazi Jewish (ASJ) AF: 0.000397 AC: 6 AN: 15120

East Asian (EAS) AF: 0.00 AC: 0 AN: 26412

South Asian (SAS) AF: 0.00 AC: 0 AN: 37168

European-Finnish (FIN) AF: 0.0000401 AC: 1 AN: 24916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3084

European-Non Finnish (NFE) AF: 0.000264 AC: 254 AN: 960724

Other (OTH) AF: 0.000174 AC: 8 AN: 45922

GnomAD4 genome AF: 0.000250 AC: 38 AN: 151770 Hom.: 0 Cov.: 33 AF XY: 0.000216 AC XY: 16 AN XY: 74122

African (AFR) AF: 0.0000725 AC: 3 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000951 AC: 1 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000457 AC: 31 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000594 Hom.: 0

Bravo AF: 0.000230

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	B3GALNT2-related disorder (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		1.6
PromoterAI		-0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	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: rs766891631; hg19: chr1-235667472;