chr17-76626782-C-A

Variant names:

• chr17-76626782-C-A
• rs752583805
• NM_018414.5:c.1180G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018414.5(ST6GALNAC1):​c.1180G>T​(p.Gly394*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST6GALNAC1 NM_018414.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.61
• Publications: 0 publications found

Genes affected

ST6GALNAC1 (HGNC:23614): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 1) Glycosylation of proteins affects cell-cell interaction, interactions with the matrix, and the functions of intracellular molecules. ST6GALNAC1 transfers a sialic acid, N-acetylneuraminic acid (NeuAc), in an alpha-2,6 linkage to O-linked GalNAc residues. The cancer-associated sialyl-Tn (sTn) antigen is formed by ST6GALNAC1-catalyzed sialylation of GalNAc residues on mucins (Ikehara et al., 1999 [PubMed 10536037]; Sewell et al., 2006 [PubMed 16319059]).[supplied by OMIM, Mar 2008]

SNHG16 (HGNC:44352): (small nucleolar RNA host gene 16)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018414.5. 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
	ST6GALNAC1	NM_018414.5	MANE Select	c.1180G>T	p.Gly394*	stop_gained	Exon 5 of 9	NP_060884.1	Q9NSC7
	ST6GALNAC1	NM_001289107.2		c.784G>T	p.Gly262*	stop_gained	Exon 6 of 10	NP_001276036.1
	ST6GALNAC1	NR_110309.2		n.1299G>T		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC1	ENST00000156626.12	TSL:1 MANE Select	c.1180G>T	p.Gly394*	stop_gained	Exon 5 of 9	ENSP00000156626.6	Q9NSC7
	ST6GALNAC1	ENST00000359088.9	TSL:1	n.1180G>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000351991.4	G3XAD9
	ST6GALNAC1	ENST00000592042.5	TSL:1	n.*1125G>T		non_coding_transcript_exon	Exon 6 of 10	ENSP00000465092.1	K7EJA8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.86
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		6.6
Vest4		0.17
GERP RS		4.8
PromoterAI		0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs752583805; hg19: chr17-74622864;