chr1-43758215-A-G

Variant names:

• chr1-43758215-A-G
• rs11579637
• NM_006279.5:c.118+21835A>G

Variant summary

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

The NM_006279.5(ST3GAL3):​c.118+21835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 149,282 control chromosomes in the GnomAD database, including 9,027 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 0.31 (9027 hom., cov: 27)
• Consequence: ST3GAL3 NM_006279.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.930
• Publications: 3 publications found

Genes affected

ST3GAL3 (HGNC:10866): (ST3 beta-galactoside alpha-2,3-sialyltransferase 3) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ST3GAL3 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 15

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• intellectual disability, autosomal recessive 12

  Inheritance: AR Classification: STRONG Submitted by: G2P
• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000284989 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006279.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL3	NM_006279.5	MANE Select	c.118+21835A>G		intron	N/A	NP_006270.1
	ST3GAL3	NM_001350619.2		c.163+21790A>G		intron	N/A	NP_001337548.1
	ST3GAL3	NM_174963.5		c.163+21790A>G		intron	N/A	NP_777623.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL3	ENST00000347631.8	TSL:5 MANE Select	c.118+21835A>G		intron	N/A	ENSP00000317192.6
	ST3GAL3	ENST00000372372.7	TSL:1	c.118+21835A>G		intron	N/A	ENSP00000361447.2
	ST3GAL3	ENST00000361746.9	TSL:1	c.118+21835A>G		intron	N/A	ENSP00000354657.5

Frequencies

GnomAD3 genomes AF: 0.315 AC: 46952 AN: 149166 Hom.: 9025 Cov.: 27

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.315 AC: 46959 AN: 149282 Hom.: 9027 Cov.: 27 AF XY: 0.313 AC XY: 22768 AN XY: 72626

African (AFR) AF: 0.0928 AC: 3778 AN: 40732

American (AMR) AF: 0.286 AC: 4295 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1268 AN: 3450

East Asian (EAS) AF: 0.540 AC: 2676 AN: 4958

South Asian (SAS) AF: 0.380 AC: 1777 AN: 4682

European-Finnish (FIN) AF: 0.381 AC: 3709 AN: 9724

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.420 AC: 28357 AN: 67440

Other (OTH) AF: 0.318 AC: 663 AN: 2084

Alfa AF: 0.354 Hom.: 1417

Bravo AF: 0.300

Asia WGS AF: 0.453 AC: 1574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.82
PhyloP100		0.93
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: rs11579637; hg19: chr1-44223886;