rs149309844

Positions:

• chr2-85847875-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000638572.2(ST3GAL5):​c.648C>T​(p.Phe216=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,613,822 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (17 hom.)
• Consequence: ST3GAL5 ENST00000638572.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.247

Genes affected

ST3GAL5 (HGNC:10872): (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The protein encoded by this gene is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-85847875-G-A is Benign according to our data. Variant chr2-85847875-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 197224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.247 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00364 (554/152136) while in subpopulation AMR AF= 0.00968 (148/15284). AF 95% confidence interval is 0.00841. There are 2 homozygotes in gnomad4. There are 260 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST3GAL5	NM_003896.4	c.648C>T	p.Phe216=	synonymous_variant	4/7	ENST00000638572.2	NP_003887.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL5	ENST00000638572.2	c.648C>T	p.Phe216=	synonymous_variant	4/7	1	NM_003896.4	ENSP00000491316	A1

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 555 AN: 152018 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00970

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00500

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00257 AC: 642 AN: 249770 Hom.: 0 AF XY: 0.00242 AC XY: 327 AN XY: 135170

Gnomad AFR exome AF: 0.000868

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.000599

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00410 AC: 5996 AN: 1461686 Hom.: 17 Cov.: 31 AF XY: 0.00391 AC XY: 2845 AN XY: 727138

Gnomad4 AFR exome AF: 0.000806

Gnomad4 AMR exome AF: 0.00344

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.00498

Gnomad4 OTH exome AF: 0.00391

GnomAD4 genome AF: 0.00364 AC: 554 AN: 152136 Hom.: 2 Cov.: 32 AF XY: 0.00350 AC XY: 260 AN XY: 74364

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00968

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000834

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00500

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00326 Hom.: 1

Bravo AF: 0.00380

EpiCase AF: 0.00403

EpiControl AF: 0.00445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 24, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	ST3GAL5: BP4, BP7 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

GM3 synthase deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 13, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.59

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: rs149309844; hg19: chr2-86074998;