chr1-43788915-G-A

Position:

• chr1-43788915-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006279.5(ST3GAL3):​c.119-3187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,380 control chromosomes in the GnomAD database, including 1,292 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 0.11 (1292 hom., cov: 30)
• Consequence: ST3GAL3 NM_006279.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST3GAL3	NM_006279.5	c.119-3187G>A		intron_variant		ENST00000347631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.119-3187G>A		intron_variant		5	NM_006279.5	A1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17208 AN: 151288 Hom.: 1290 Cov.: 30

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.000970

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.114 AC: 17204 AN: 151380 Hom.: 1292 Cov.: 30 AF XY: 0.112 AC XY: 8247 AN XY: 73928

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.000973

Gnomad4 SAS AF: 0.0509

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.129

Alfa AF: 0.143 Hom.: 889

Bravo AF: 0.108

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs12741964; hg19: chr1-44254586;