rs1404629390

Variant names:

• chr17-76574367-T-C
• rs1404629390
• NM_006456.3:c.359A>G

Variant summary

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

The NM_006456.3(ST6GALNAC2):​c.359A>G​(p.Gln120Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ST6GALNAC2 NM_006456.3 missense, splice_region
• Scores: Splicing: ADA: 0.0004528
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32
• Publications: 0 publications found

Genes affected

ST6GALNAC2 (HGNC:10867): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 2) ST6GALNAC2 belongs to a family of sialyltransferases that add sialic acids to the nonreducing ends of glycoconjugates. At the cell surface, these modifications have roles in cell-cell and cell-substrate interactions, bacterial adhesion, and protein targeting (Samyn-Petit et al., 2000 [PubMed 10742600]).[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=0.18585026).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006456.3. 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
	ST6GALNAC2	NM_006456.3	MANE Select	c.359A>G	p.Gln120Arg	missense splice_region	Exon 3 of 9	NP_006447.2	Q9UJ37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC2	ENST00000225276.10	TSL:1 MANE Select	c.359A>G	p.Gln120Arg	missense splice_region	Exon 3 of 9	ENSP00000225276.4	Q9UJ37
	ST6GALNAC2	ENST00000909969.1		c.359A>G	p.Gln120Arg	missense splice_region	Exon 3 of 9	ENSP00000580028.1
	ST6GALNAC2	ENST00000943099.1		c.359A>G	p.Gln120Arg	missense splice_region	Exon 3 of 9	ENSP00000613158.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000808 AC: 2 AN: 247528 AF XY: 0.00000745

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459376 Hom.: 0 Cov.: 41 AF XY: 0.00000689 AC XY: 5 AN XY: 725798

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.0000225 AC: 1 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110732

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000659 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.068
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.088
Sift	Benign	0.32	T
Sift4G	Benign	0.39	T
Polyphen		0.15	B
Vest4		0.083
MutPred		0.55		Gain of MoRF binding (P = 0.019)
MVP		0.33
MPC		0.19
ClinPred		0.16	T
GERP RS		4.5
Varity_R		0.31
gMVP		0.35
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00045
dbscSNV1_RF	Benign	0.060
SpliceAI score (max)		0.040		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: rs1404629390; hg19: chr17-74570449;