rs149309844

Variant names:

• chr2-85847875-G-A
• rs149309844
• NM_003896.4:c.648C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001354247.1(ST3GAL5):​c.-257C>T variant causes a 5 prime UTR premature start codon gain 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 NM_001354247.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.247
• Publications: 0 publications found

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]

ST3GAL5 Gene-Disease associations (from GenCC):

• GM3 synthase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -20 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 Benign/Likely_benign. ClinVar VariationId is 197224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354247.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	NM_003896.4	MANE Select	c.648C>T	p.Phe216Phe	synonymous	Exon 4 of 7	NP_003887.3
	ST3GAL5	NM_001354247.1		c.-257C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_001341176.1
	ST3GAL5	NM_001042437.2		c.579C>T	p.Phe193Phe	synonymous	Exon 4 of 7	NP_001035902.1	Q9UNP4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	ENST00000638572.2	TSL:1 MANE Select	c.648C>T	p.Phe216Phe	synonymous	Exon 4 of 7	ENSP00000491316.1	Q9UNP4-1
	ST3GAL5	ENST00000393808.8	TSL:1	c.579C>T	p.Phe193Phe	synonymous	Exon 4 of 7	ENSP00000377397.3	Q9UNP4-3
	ST3GAL5	ENST00000393805.6	TSL:1	c.564C>T	p.Phe188Phe	synonymous	Exon 4 of 7	ENSP00000377394.1	Q9UNP4-2

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

GnomAD2 exomes AF: 0.00257 AC: 642 AN: 249770 AF XY: 0.00242

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 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

African (AFR) AF: 0.000806 AC: 27 AN: 33480

American (AMR) AF: 0.00344 AC: 154 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86228

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53252

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00498 AC: 5537 AN: 1112004

Other (OTH) AF: 0.00391 AC: 236 AN: 60396

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

African (AFR) AF: 0.00106 AC: 44 AN: 41488

American (AMR) AF: 0.00968 AC: 148 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000834 AC: 4 AN: 4796

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00500 AC: 340 AN: 67998

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00332 Hom.: 1

Bravo AF: 0.00380

EpiCase AF: 0.00403

EpiControl AF: 0.00445

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	GM3 synthase deficiency (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.59
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism

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: rs149309844; hg19: chr2-86074998;