17-76626308-T-C

Variant names:

• chr17-76626308-T-C
• NM_018414.5:c.1396A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018414.5(ST6GALNAC1):​c.1396A>G​(p.Lys466Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST6GALNAC1 NM_018414.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.577
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090548664).

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.1396A>G	p.Lys466Glu	missense	Exon 6 of 9	NP_060884.1	Q9NSC7
	ST6GALNAC1	NM_001289107.2		c.1000A>G	p.Lys334Glu	missense	Exon 7 of 10	NP_001276036.1
	ST6GALNAC1	NR_110309.2		n.1431-213A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC1	ENST00000156626.12	TSL:1 MANE Select	c.1396A>G	p.Lys466Glu	missense	Exon 6 of 9	ENSP00000156626.6	Q9NSC7
	ST6GALNAC1	ENST00000592042.5	TSL:1	n.*1341A>G		non_coding_transcript_exon	Exon 7 of 10	ENSP00000465092.1	K7EJA8
	ST6GALNAC1	ENST00000592042.5	TSL:1	n.*1341A>G		3_prime_UTR	Exon 7 of 10	ENSP00000465092.1	K7EJA8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.52
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.72	N
PhyloP100		0.58
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.075
Sift	Benign	0.54	T
Sift4G	Benign	0.74	T
Polyphen		0.24	B
Vest4		0.23
MutPred		0.63		Loss of MoRF binding (P = 0.0145)
MVP		0.19
MPC		0.22
ClinPred		0.16	T
GERP RS		0.44
Varity_R		0.094
gMVP		0.73

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

hg19: chr17-74622390;