chr17-76626728-C-A

Variant names:

• chr17-76626728-C-A
• NM_018414.5:c.1234G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018414.5(ST6GALNAC1):​c.1234G>T​(p.Gly412Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,874 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G412S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ST6GALNAC1 NM_018414.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GALNAC1	NM_018414.5	c.1234G>T	p.Gly412Cys	missense_variant	Exon 5 of 9	ENST00000156626.12	NP_060884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GALNAC1	ENST00000156626.12	c.1234G>T	p.Gly412Cys	missense_variant	Exon 5 of 9	1	NM_018414.5	ENSP00000156626.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.0025	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-7.1	D;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.027	D;.
Sift4G	Uncertain	0.025	D;.
Polyphen		1.0	D;.
Vest4		0.72
MutPred		0.78		Loss of sheet (P = 0.1158);.;
MVP		0.13
MPC		0.53
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.63
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-74622810;