chr18-46686213-C-T

Position:

• chr18-46686213-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_013305.6(ST8SIA5):​c.530G>A​(p.Arg177His) variant causes a missense change. The variant allele was found at a frequency of 0.000906 in 1,614,144 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (5 hom.)
• Consequence: ST8SIA5 NM_013305.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.62

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010541379).
• BP6: Variant 18-46686213-C-T is Benign according to our data. Variant chr18-46686213-C-T is described in ClinVar as [Benign]. Clinvar id is 768932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0047 (716/152250) while in subpopulation AFR AF= 0.0168 (696/41550). AF 95% confidence interval is 0.0157. There are 8 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA5	NM_013305.6	c.530G>A	p.Arg177His	missense_variant	5/7	ENST00000315087.12	NP_037437.2
ST8SIA5	NM_001307986.2	c.638G>A	p.Arg213His	missense_variant	6/8		NP_001294915.1
ST8SIA5	NM_001307987.2	c.437G>A	p.Arg146His	missense_variant	4/6		NP_001294916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA5	ENST00000315087.12	c.530G>A	p.Arg177His	missense_variant	5/7	1	NM_013305.6	ENSP00000321343	P4

Frequencies

GnomAD3 genomes AF: 0.00471 AC: 717 AN: 152132 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00127 AC: 320 AN: 251484 Hom.: 3 AF XY: 0.000802 AC XY: 109 AN XY: 135918

Gnomad AFR exome AF: 0.0177

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000510 AC: 746 AN: 1461894 Hom.: 5 Cov.: 31 AF XY: 0.000433 AC XY: 315 AN XY: 727248

Gnomad4 AFR exome AF: 0.0165

Gnomad4 AMR exome AF: 0.000402

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.00470 AC: 716 AN: 152250 Hom.: 8 Cov.: 32 AF XY: 0.00421 AC XY: 313 AN XY: 74416

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000675 Hom.: 1

Bravo AF: 0.00528

ESP6500AA AF: 0.0184 AC: 81

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00162 AC: 197

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.60
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	.;T;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	T;D;D
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;L;.
MutationTaster	Benign	0.77	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.097	T;T;T
Polyphen		0.96, 0.96	.;D;D
Vest4		0.38
MVP		0.52
MPC		1.4
ClinPred		0.047	T
GERP RS		4.5
Varity_R		0.071
gMVP		0.36

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: rs115206837; hg19: chr18-44266176;