chr12-4760762-A-G

Variant names:

• chr12-4760762-A-G
• rs2286580
• NM_017417.2:c.1174-196A>G

Variant summary

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

The NM_017417.2(GALNT8):​c.1174-196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,996 control chromosomes in the GnomAD database, including 11,562 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 0.39 (11562 hom., cov: 31)
• Consequence: GALNT8 NM_017417.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 4 publications found

Genes affected

GALNT8 (HGNC:4130): (polypeptide N-acetylgalactosaminyltransferase 8) This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. [provided by RefSeq, Jul 2008]

ENSG00000255639 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017417.2. 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
	GALNT8	NM_017417.2	MANE Select	c.1174-196A>G		intron	N/A	NP_059113.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT8	ENST00000252318.7	TSL:1 MANE Select	c.1174-196A>G		intron	N/A	ENSP00000252318.2
	ENSG00000255639	ENST00000648836.1		c.964-196A>G		intron	N/A	ENSP00000497305.1
	GALNT8	ENST00000902363.1		c.1171-196A>G		intron	N/A	ENSP00000572422.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58590 AN: 151878 Hom.: 11554 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.386 AC: 58631 AN: 151996 Hom.: 11562 Cov.: 31 AF XY: 0.384 AC XY: 28548 AN XY: 74298

African (AFR) AF: 0.326 AC: 13505 AN: 41454

American (AMR) AF: 0.441 AC: 6738 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3468

East Asian (EAS) AF: 0.364 AC: 1875 AN: 5158

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4818

European-Finnish (FIN) AF: 0.403 AC: 4263 AN: 10576

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28581 AN: 67942

Other (OTH) AF: 0.348 AC: 735 AN: 2110

Alfa AF: 0.394 Hom.: 2033

Bravo AF: 0.388

Asia WGS AF: 0.288 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		-0.083
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: rs2286580; hg19: chr12-4869928; COSMIC: COSV52901548; COSMIC: COSV52901548;