12-4754142-G-C

Variant names:

• chr12-4754142-G-C
• rs10849138
• NM_017417.2:c.1174-6816G>C

Variant summary

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

The NM_017417.2(GALNT8):​c.1174-6816G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,956 control chromosomes in the GnomAD database, including 21,132 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 0.52 (21132 hom., cov: 31)
• Consequence: GALNT8 NM_017417.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT8	NM_017417.2	c.1174-6816G>C		intron_variant	Intron 6 of 10	ENST00000252318.7	NP_059113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT8	ENST00000252318.7	c.1174-6816G>C		intron_variant	Intron 6 of 10	1	NM_017417.2	ENSP00000252318.2
ENSG00000255639	ENST00000648836.1	c.964-6816G>C		intron_variant	Intron 10 of 14			ENSP00000497305.1
GALNT8	ENST00000648865.1	n.26-6816G>C		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79052 AN: 151840 Hom.: 21121 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.521 AC: 79102 AN: 151956 Hom.: 21132 Cov.: 31 AF XY: 0.516 AC XY: 38312 AN XY: 74252

African (AFR) AF: 0.428 AC: 17748 AN: 41440

American (AMR) AF: 0.557 AC: 8498 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1838 AN: 3464

East Asian (EAS) AF: 0.367 AC: 1882 AN: 5134

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4820

European-Finnish (FIN) AF: 0.552 AC: 5828 AN: 10560

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40082 AN: 67956

Other (OTH) AF: 0.494 AC: 1042 AN: 2108

Alfa AF: 0.437 Hom.: 1313

Bravo AF: 0.519

Asia WGS AF: 0.334 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.44
PhyloP100		-1.1
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: rs10849138; hg19: chr12-4863308;