rs752875565

Variant names:

• chr17-76625364-C-A
• rs752875565
• NM_018414.5:c.1769G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-76625364-C-A
• chr17-76625364-C-G
• chr17-76625364-C-T

Variant summary

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

The NM_018414.5(ST6GALNAC1):​c.1769G>T​(p.Arg590Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R590H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ST6GALNAC1 NM_018414.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• 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.1769G>T	p.Arg590Leu	missense	Exon 9 of 9	NP_060884.1	Q9NSC7
	ST6GALNAC1	NM_001289107.2		c.1373G>T	p.Arg458Leu	missense	Exon 10 of 10	NP_001276036.1
	ST6GALNAC1	NR_110309.2		n.1784G>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC1	ENST00000156626.12	TSL:1 MANE Select	c.1769G>T	p.Arg590Leu	missense	Exon 9 of 9	ENSP00000156626.6	Q9NSC7
	ST6GALNAC1	ENST00000359088.9	TSL:1	n.*249G>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000351991.4	G3XAD9
	ST6GALNAC1	ENST00000592042.5	TSL:1	n.*1714G>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000465092.1	K7EJA8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461544 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5514

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.8
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.73		Loss of MoRF binding (P = 0.007)
MVP		0.57
MPC		0.58
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.78
gMVP		0.71

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: rs752875565; hg19: chr17-74621446;