rs757247613

Variant names:

• chr18-46686187-C-A
• NM_013305.6:c.556G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-46686187-C-A
• chr18-46686187-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_013305.6(ST8SIA5):​c.556G>T​(p.Asp186Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D186N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST8SIA5 NM_013305.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.45

Genes affected

ST8SIA5 (HGNC:17827): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 5) The protein encoded by this gene is a type II membrane protein that may be present in the Golgi apparatus. The encoded protein, which is a member of glycosyltransferase family 29, may be involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, and GT3 from GD1a, GT1b, GM1b, and GD3, respectively. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA5	NM_013305.6	c.556G>T	p.Asp186Tyr	missense_variant	Exon 5 of 7	ENST00000315087.12	NP_037437.2
ST8SIA5	NM_001307986.2	c.664G>T	p.Asp222Tyr	missense_variant	Exon 6 of 8		NP_001294915.1
ST8SIA5	NM_001307987.2	c.463G>T	p.Asp155Tyr	missense_variant	Exon 4 of 6		NP_001294916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA5	ENST00000315087.12	c.556G>T	p.Asp186Tyr	missense_variant	Exon 5 of 7	1	NM_013305.6	ENSP00000321343.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	.;T;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Pathogenic	3.8	.;H;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.9	D;D;D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.98
MutPred		0.84		Loss of stability (P = 0.102);.;.;
MVP		0.86
MPC		1.6
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.90
gMVP		0.92

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: chr18-44266150;