2-85840003-ATT-ATTTT

Variant names:

• chr2-85840003-A-ATT
• rs550737011
• NM_003896.4:c.*139_*140dupAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003896.4(ST3GAL5):​c.*139_*140dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000841 in 1,189,442 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: ST3GAL5 NM_003896.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003896.4. 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.*139_*140dupAA		3_prime_UTR	Exon 7 of 7	NP_003887.3
	ST3GAL5	NM_001042437.2		c.*139_*140dupAA		3_prime_UTR	Exon 7 of 7	NP_001035902.1	Q9UNP4-3
	ST3GAL5	NM_001354227.2		c.*139_*140dupAA		3_prime_UTR	Exon 8 of 8	NP_001341156.1	A0A0S2Z4S6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	ENST00000638572.2	TSL:1 MANE Select	c.*139_*140dupAA		3_prime_UTR	Exon 7 of 7	ENSP00000491316.1	Q9UNP4-1
	ST3GAL5	ENST00000393808.8	TSL:1	c.*139_*140dupAA		3_prime_UTR	Exon 7 of 7	ENSP00000377397.3	Q9UNP4-3
	ST3GAL5	ENST00000393805.6	TSL:1	c.*139_*140dupAA		3_prime_UTR	Exon 7 of 7	ENSP00000377394.1	Q9UNP4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.41e-7 AC: 1 AN: 1189442 Hom.: 0 Cov.: 17 AF XY: 0.00000170 AC XY: 1 AN XY: 589274

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26178

American (AMR) AF: 0.00 AC: 0 AN: 28132

Ashkenazi Jewish (ASJ) AF: 0.0000450 AC: 1 AN: 22238

East Asian (EAS) AF: 0.00 AC: 0 AN: 34642

South Asian (SAS) AF: 0.00 AC: 0 AN: 69492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4070

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 916500

Other (OTH) AF: 0.00 AC: 0 AN: 50564

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.040

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs550737011; hg19: chr2-86067126;