NM_004481.5:c.127-18176A>T

Variant names:

• chr1-230160042-A-T
• rs10127775
• NM_004481.5:c.127-18176A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004481.5(GALNT2):​c.127-18176A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,964 control chromosomes in the GnomAD database, including 18,285 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (18285 hom., cov: 31)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 28 publications found

Genes affected

GALNT2 (HGNC:4124): (polypeptide N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 2 protein family. Members of this family initiate mucin-type O-glycoslation of peptides in the Golgi apparatus. The encoded protein may be involved in O-linked glycosylation of the immunoglobulin A1 hinge region. This gene may influence triglyceride levels, and may be involved Type 2 diabetes, as well as several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GALNT2 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type iit

  Inheritance: AR Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004481.5. 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
	GALNT2	NM_004481.5	MANE Select	c.127-18176A>T		intron	N/A	NP_004472.1
	GALNT2	NM_001291866.2		c.13-18176A>T		intron	N/A	NP_001278795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT2	ENST00000366672.5	TSL:1 MANE Select	c.127-18176A>T		intron	N/A	ENSP00000355632.4
	GALNT2	ENST00000935982.1		c.127-18176A>T		intron	N/A	ENSP00000606041.1
	GALNT2	ENST00000950855.1		c.127-18176A>T		intron	N/A	ENSP00000620914.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68031 AN: 151844 Hom.: 18279 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.448 AC: 68044 AN: 151964 Hom.: 18285 Cov.: 31 AF XY: 0.445 AC XY: 33024 AN XY: 74274

African (AFR) AF: 0.138 AC: 5707 AN: 41426

American (AMR) AF: 0.554 AC: 8467 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1195 AN: 5160

South Asian (SAS) AF: 0.423 AC: 2031 AN: 4800

European-Finnish (FIN) AF: 0.538 AC: 5690 AN: 10576

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41048 AN: 67938

Other (OTH) AF: 0.506 AC: 1066 AN: 2108

Alfa AF: 0.406 Hom.: 1380

Bravo AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.77
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs10127775; hg19: chr1-230295789;