NM_018414.5:c.1234G>A

Variant names:

• chr17-76626728-C-T
• rs138031739
• NM_018414.5:c.1234G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018414.5(ST6GALNAC1):​c.1234G>A​(p.Gly412Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,614,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: ST6GALNAC1 NM_018414.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18026403).

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.1234G>A	p.Gly412Ser	missense	Exon 5 of 9	NP_060884.1	Q9NSC7
	ST6GALNAC1	NM_001289107.2		c.838G>A	p.Gly280Ser	missense	Exon 6 of 10	NP_001276036.1
	ST6GALNAC1	NR_110309.2		n.1353G>A		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.1234G>A	p.Gly412Ser	missense	Exon 5 of 9	ENSP00000156626.6	Q9NSC7
	ST6GALNAC1	ENST00000359088.9	TSL:1	n.1234G>A		non_coding_transcript_exon	Exon 5 of 8	ENSP00000351991.4	G3XAD9
	ST6GALNAC1	ENST00000592042.5	TSL:1	n.*1179G>A		non_coding_transcript_exon	Exon 6 of 10	ENSP00000465092.1	K7EJA8

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.0000994 AC: 25 AN: 251490 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000595 AC: 87 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.0000550 AC XY: 40 AN XY: 727238

African (AFR) AF: 0.00146 AC: 49 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111998

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.000401 AC: 61 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74454

African (AFR) AF: 0.00130 AC: 54 AN: 41562

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000381 Hom.: 0

Bravo AF: 0.000434

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000988 AC: 12

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	Uncertain	0.39
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.27
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.56
MVP		0.14
MPC		0.51
ClinPred		0.21	T
GERP RS		4.8
PromoterAI		-0.051	Neutral
Varity_R		0.43
gMVP		0.84
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs138031739; hg19: chr17-74622810;