rs6778436

Variant names:

• chr3-186966576-T-A
• rs6778436
• NM_173216.2:c.-183+2650T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173216.2(ST6GAL1):​c.-183+2650T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 152,278 control chromosomes in the GnomAD database, including 689 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.065 (689 hom., cov: 32)
• Consequence: ST6GAL1 NM_173216.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 3 publications found

Genes affected

ST6GAL1 (HGNC:10860): (ST6 beta-galactoside alpha-2,6-sialyltransferase 1) This gene encodes a member of glycosyltransferase family 29. The encoded protein is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The protein, which is normally found in the Golgi but can be proteolytically processed to a soluble form, is involved in the generation of the cell-surface carbohydrate determinants and differentiation antigens HB-6, CD75, and CD76. This gene has been incorrectly referred to as CD75. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GAL1	NM_173216.2	c.-183+2650T>A		intron_variant	Intron 2 of 7	ENST00000169298.8	NP_775323.1
ST6GAL1	NM_173217.2	c.-219+2650T>A		intron_variant	Intron 2 of 6		NP_775324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GAL1	ENST00000169298.8	c.-183+2650T>A		intron_variant	Intron 2 of 7	1	NM_173216.2	ENSP00000169298.3

Frequencies

GnomAD3 genomes AF: 0.0648 AC: 9859 AN: 152160 Hom.: 686 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0425

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0649 AC: 9879 AN: 152278 Hom.: 689 Cov.: 32 AF XY: 0.0653 AC XY: 4863 AN XY: 74454

African (AFR) AF: 0.177 AC: 7342 AN: 41544

American (AMR) AF: 0.0647 AC: 990 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4828

European-Finnish (FIN) AF: 0.0557 AC: 591 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 751 AN: 68012

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0427 Hom.: 49

Bravo AF: 0.0691

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs6778436; hg19: chr3-186684364;