12-51360295-C-T

Position:

• chr12-51360295-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007210.4(GALNT6):​c.1167+426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 153,354 control chromosomes in the GnomAD database, including 5,539 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 0.27 (5501 hom., cov: 31)
  • Exomes 𝑓: 0.23 (38 hom.)
• Consequence: GALNT6 NM_007210.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658

Genes affected

GALNT6 (HGNC:4128): (polypeptide N-acetylgalactosaminyltransferase 6) 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. The encoded protein is capable of glycosylating fibronectin peptide in vitro and is expressed in a fibroblast cell line, indicating that it may be involved in the synthesis of oncofetal fibronectin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT6	NM_007210.4	c.1167+426G>A		intron_variant		ENST00000356317.8	NP_009141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT6	ENST00000356317.8	c.1167+426G>A		intron_variant		1	NM_007210.4	ENSP00000348668.2
GALNT6	ENST00000543196.6	c.1167+426G>A		intron_variant		1		ENSP00000444171.1
GALNT6	ENST00000603641.1	n.1050-963G>A		intron_variant		1		ENSP00000474670.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40272 AN: 151780 Hom.: 5499 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.230 AC: 335 AN: 1456 Hom.: 38 AF XY: 0.231 AC XY: 172 AN XY: 744

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.0984

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0714

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.265 AC: 40306 AN: 151898 Hom.: 5501 Cov.: 31 AF XY: 0.262 AC XY: 19453 AN XY: 74236

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.254

Alfa AF: 0.265 Hom.: 4554

Bravo AF: 0.259

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	16
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs4761874; hg19: chr12-51754079;