3-186933001-A-G

Variant names:

• chr3-186933001-A-G
• rs10937275
• NM_173216.2:c.-325+2167A>G

Variant summary

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

The NM_173216.2(ST6GAL1):​c.-325+2167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,210 control chromosomes in the GnomAD database, including 60,060 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 0.89 (60060 hom., cov: 31)
• Consequence: ST6GAL1 NM_173216.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 24 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GAL1	NM_173216.2	c.-325+2167A>G		intron_variant	Intron 1 of 7	ENST00000169298.8	NP_775323.1
ST6GAL1	NM_173217.2	c.-361+2167A>G		intron_variant	Intron 1 of 6		NP_775324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GAL1	ENST00000169298.8	c.-325+2167A>G		intron_variant	Intron 1 of 7	1	NM_173216.2	ENSP00000169298.3

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135027 AN: 152092 Hom.: 60018 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.888 AC: 135127 AN: 152210 Hom.: 60060 Cov.: 31 AF XY: 0.891 AC XY: 66277 AN XY: 74422

African (AFR) AF: 0.863 AC: 35838 AN: 41516

American (AMR) AF: 0.932 AC: 14254 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3161 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5180

South Asian (SAS) AF: 0.978 AC: 4728 AN: 4832

European-Finnish (FIN) AF: 0.862 AC: 9121 AN: 10586

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59881 AN: 68024

Other (OTH) AF: 0.916 AC: 1930 AN: 2106

Alfa AF: 0.888 Hom.: 261182

Bravo AF: 0.890

Asia WGS AF: 0.981 AC: 3413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-2.0
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: rs10937275; hg19: chr3-186650790;