NM_001323368.2:c.967A>C

Variant names:

• chr3-98793732-A-C
• rs143530286
• NM_001323368.2:c.967A>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001323368.2(ST3GAL6):​c.967A>C​(p.Asn323His) variant causes a missense change. The variant allele was found at a frequency of 0.00000873 in 1,604,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N323S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ST3GAL6 NM_001323368.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

Genes affected

ST3GAL6 (HGNC:18080): (ST3 beta-galactoside alpha-2,3-sialyltransferase 6) The protein encoded by this gene is a member of the sialyltransferase family. Members of this family are enzymes that transfer sialic acid from the activated cytidine 5'-monophospho-N-acetylneuraminic acid to terminal positions on sialylated glycolipids (gangliosides) or to the N- or O-linked sugar chains of glycoproteins. This protein has high specificity for neolactotetraosylceramide and neolactohexaosylceramide as glycolipid substrates and may contribute to the formation of selectin ligands and sialyl Lewis X, a carbohydrate important for cell-to-cell recognition and a blood group antigen. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30790645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323368.2. 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
	ST3GAL6	NM_001323368.2	MANE Select	c.967A>C	p.Asn323His	missense	Exon 10 of 10	NP_001310297.1	Q9Y274-1
	ST3GAL6	NM_001271145.2		c.1126A>C	p.Asn376His	missense	Exon 10 of 10	NP_001258074.1	A0A087WXB8
	ST3GAL6	NM_001271146.2		c.967A>C	p.Asn323His	missense	Exon 10 of 10	NP_001258075.1	Q9Y274-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL6	ENST00000483910.6	TSL:1 MANE Select	c.967A>C	p.Asn323His	missense	Exon 10 of 10	ENSP00000417376.1	Q9Y274-1
	ST3GAL6	ENST00000394162.5	TSL:1	c.967A>C	p.Asn323His	missense	Exon 11 of 11	ENSP00000377717.1	Q9Y274-1
	ST3GAL6	ENST00000613264.5	TSL:1	c.967A>C	p.Asn323His	missense	Exon 10 of 10	ENSP00000480884.2	Q9Y274-1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 244600 AF XY: 0.00000756

Gnomad AFR exome AF: 0.000187

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1452064 Hom.: 0 Cov.: 28 AF XY: 0.00000416 AC XY: 3 AN XY: 721898

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000120 AC: 4 AN: 33208

American (AMR) AF: 0.00 AC: 0 AN: 42976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39354

South Asian (SAS) AF: 0.00 AC: 0 AN: 83586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107808

Other (OTH) AF: 0.00 AC: 0 AN: 60082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00828108), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74336

African (AFR) AF: 0.000217 AC: 9 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

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

Alfa AF: 0.0000649 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

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	0.090
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.12	T
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.40
MVP		0.51
MPC		0.64
ClinPred		0.23	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.36
Mutation Taster		=90/10	polymorphism

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: rs143530286; hg19: chr3-98512576;