rs149296455

Variant names:

• chr11-45806335-C-T
• rs149296455
• NM_018389.5:c.534C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-45806335-C-T
• chr11-45806335-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP7 BS1_Supporting

The NM_018389.5(SLC35C1):​c.534C>T​(p.Ile178Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,612,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: SLC35C1 NM_018389.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.001348
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.13
• Publications: 0 publications found

Genes affected

SLC35C1 (HGNC:20197): (solute carrier family 35 member C1) This gene encodes a GDP-fucose transporter that is found in the Golgi apparatus. Mutations in this gene result in congenital disorder of glycosylation type IIc. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

SLC35C1 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency type II

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-3.13 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000361 (55/152302) while in subpopulation AFR AF = 0.0012 (50/41572). AF 95% confidence interval is 0.000937. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018389.5. 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
	SLC35C1	NM_018389.5	MANE Select	c.534C>T	p.Ile178Ile	splice_region synonymous	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_001425155.1		c.534C>T	p.Ile178Ile	splice_region synonymous	Exon 2 of 3	NP_001412084.1	B3KQH0
	SLC35C1	NM_001145265.2		c.495C>T	p.Ile165Ile	splice_region synonymous	Exon 2 of 3	NP_001138737.1	Q96A29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.534C>T	p.Ile178Ile	splice_region synonymous	Exon 1 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000442528.2	TSL:1	c.495C>T	p.Ile165Ile	splice_region synonymous	Exon 2 of 3	ENSP00000412408.2	Q96A29-2
	SLC35C1	ENST00000953729.1		c.534C>T	p.Ile178Ile	splice_region synonymous	Exon 2 of 3	ENSP00000623788.1

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 249068 AF XY: 0.0000741

Gnomad AFR exome AF: 0.00112

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1460162 Hom.: 0 Cov.: 35 AF XY: 0.0000262 AC XY: 19 AN XY: 726394

African (AFR) AF: 0.000747 AC: 25 AN: 33478

American (AMR) AF: 0.000268 AC: 12 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111956

Other (OTH) AF: 0.000199 AC: 12 AN: 60376

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74478

African (AFR) AF: 0.00120 AC: 50 AN: 41572

American (AMR) AF: 0.000261 AC: 4 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000147 Hom.: 0

Bravo AF: 0.000472

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Leukocyte adhesion deficiency type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.39
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: rs149296455; hg19: chr11-45827886;