2-85847977-G-T

Variant names:

• chr2-85847977-G-T
• NM_003896.4:c.546C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003896.4(ST3GAL5):​c.546C>A​(p.Asp182Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ST3GAL5 NM_003896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20058233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL5	NM_003896.4	c.546C>A	p.Asp182Glu	missense_variant	Exon 4 of 7	ENST00000638572.2	NP_003887.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL5	ENST00000638572.2	c.546C>A	p.Asp182Glu	missense_variant	Exon 4 of 7	1	NM_003896.4	ENSP00000491316.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.546C>A (p.D182E) alteration is located in exon 4 (coding exon 4) of the ST3GAL5 gene. This alteration results from a C to A substitution at nucleotide position 546, causing the aspartic acid (D) at amino acid position 182 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.20	T;.;.;.;.;.;.;.;.;.;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T;T;.;.;T;T;T;.;.;.;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.98	.;N;N;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.069
Sift	Benign	0.27	.;T;T;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.67	.;T;T;.;.;.;.;.;.;.;.;.
Polyphen		0.55	P;B;B;B;.;.;.;B;B;B;.;B
Vest4		0.13, 0.14
MutPred		0.48		Gain of disorder (P = 0.0834);.;.;.;.;Gain of disorder (P = 0.0834);.;.;.;.;.;.;
MVP		0.014
MPC		0.66
ClinPred		0.29	T
GERP RS		3.7
Varity_R		0.050
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-86075100;