18-46686213-C-T

Variant names:

• chr18-46686213-C-T
• rs115206837
• NM_013305.6:c.530G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013305.6. 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
	ST8SIA5	NM_013305.6	MANE Select	c.530G>A	p.Arg177His	missense	Exon 5 of 7	NP_037437.2
	ST8SIA5	NM_001307986.2		c.638G>A	p.Arg213His	missense	Exon 6 of 8	NP_001294915.1	O15466-2
	ST8SIA5	NM_001307987.2		c.437G>A	p.Arg146His	missense	Exon 4 of 6	NP_001294916.1	F5H8D1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA5	ENST00000315087.12	TSL:1 MANE Select	c.530G>A	p.Arg177His	missense	Exon 5 of 7	ENSP00000321343.6	O15466-1
	ST8SIA5	ENST00000538168.5	TSL:2	c.638G>A	p.Arg213His	missense	Exon 6 of 8	ENSP00000445492.1	O15466-2
	ST8SIA5	ENST00000911623.1		c.623G>A	p.Arg208His	missense	Exon 6 of 8	ENSP00000581682.1

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

GnomAD2 exomes AF: 0.00127 AC: 320 AN: 251484 AF XY: 0.000802

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 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

African (AFR) AF: 0.0165 AC: 553 AN: 33480

American (AMR) AF: 0.000402 AC: 18 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000103 AC: 114 AN: 1112012

Other (OTH) AF: 0.000729 AC: 44 AN: 60396

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

African (AFR) AF: 0.0168 AC: 696 AN: 41550

American (AMR) AF: 0.000523 AC: 8 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68012

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00141 Hom.: 3

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.045
Sift	Benign	0.10	T
Sift4G	Benign	0.097	T
Polyphen		0.96	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
Mutation Taster		=85/15	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: rs115206837; hg19: chr18-44266176;