rs145613857

Variant names:

• chr11-45811294-C-T
• rs145613857
• NM_018389.5:c.1054C>T
• SLC35C1 p.Pro352Ser

Your query was ambiguous. Multiple possible variants found:

• chr11-45811294-C-T
• chr11-45811294-C-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_018389.5(SLC35C1):​c.1054C>T​(p.Pro352Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,556,504 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P352H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (17 hom.)
• Consequence: SLC35C1 NM_018389.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:8
• Conservation: PhyloP100: 1.54
• Publications: 6 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, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004312724).
• BP6: Variant 11-45811294-C-T is Benign according to our data. Variant chr11-45811294-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 252721.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00379 (578/152328) while in subpopulation NFE AF = 0.006 (408/68018). AF 95% confidence interval is 0.00552. There are 3 homozygotes in GnomAd4. There are 254 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.1054C>T	p.Pro352Ser	missense	Exon 2 of 2	NP_060859.4
	SLC35C1	NM_001425155.1		c.1054C>T	p.Pro352Ser	missense	Exon 3 of 3	NP_001412084.1	B3KQH0
	SLC35C1	NM_001145265.2		c.1015C>T	p.Pro339Ser	missense	Exon 3 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.1054C>T	p.Pro352Ser	missense	Exon 2 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000442528.2	TSL:1	c.1015C>T	p.Pro339Ser	missense	Exon 3 of 3	ENSP00000412408.2	Q96A29-2
	SLC35C1	ENST00000953729.1		c.1054C>T	p.Pro352Ser	missense	Exon 3 of 3	ENSP00000623788.1

Frequencies

GnomAD3 genomes AF: 0.00380 AC: 578 AN: 152210 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00600

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00380 AC: 738 AN: 193980 AF XY: 0.00392

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.00324

Gnomad ASJ exome AF: 0.00556

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00322

Gnomad NFE exome AF: 0.00578

Gnomad OTH exome AF: 0.00448

GnomAD4 exome AF: 0.00517 AC: 7262 AN: 1404176 Hom.: 17 Cov.: 36 AF XY: 0.00504 AC XY: 3502 AN XY: 694254

African (AFR) AF: 0.000724 AC: 23 AN: 31748

American (AMR) AF: 0.00317 AC: 120 AN: 37818

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 127 AN: 23196

East Asian (EAS) AF: 0.00 AC: 0 AN: 39182

South Asian (SAS) AF: 0.000277 AC: 22 AN: 79504

European-Finnish (FIN) AF: 0.00289 AC: 117 AN: 40488

Middle Eastern (MID) AF: 0.00125 AC: 6 AN: 4808

European-Non Finnish (NFE) AF: 0.00604 AC: 6577 AN: 1089498

Other (OTH) AF: 0.00466 AC: 270 AN: 57934

GnomAD4 genome AF: 0.00379 AC: 578 AN: 152328 Hom.: 3 Cov.: 33 AF XY: 0.00341 AC XY: 254 AN XY: 74496

African (AFR) AF: 0.00108 AC: 45 AN: 41590

American (AMR) AF: 0.00379 AC: 58 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00600 AC: 408 AN: 68018

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00365 Hom.: 4

Bravo AF: 0.00364

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	1	1	Leukocyte adhesion deficiency type II (2)
-	-	1	Intellectual disability (1)
-	-	1	not specified (1)
-	-	1	SLC35C1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.088
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.057
Sift	Benign	0.50	T
Sift4G	Benign	0.80	T
Varity_R		0.063
gMVP		0.53
Mutation Taster		=93/7	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs145613857;

hg19: chr11-45832845;