rs141379070

Variant names:

• chr11-45806323-C-T
• rs141379070
• NM_018389.5:c.522C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_018389.5(SLC35C1):​c.522C>T​(p.Cys174Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,612,664 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (13 hom.)
• Consequence: SLC35C1 NM_018389.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.277
• Publications: 1 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 11-45806323-C-T is Benign according to our data. Variant chr11-45806323-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 304739.
• BP7: Synonymous conserved (PhyloP=-0.277 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00273 (415/152248) while in subpopulation NFE AF = 0.0024 (163/67998). AF 95% confidence interval is 0.0021. There are 1 homozygotes in GnomAd4. There are 237 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 13 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	NM_018389.5	MANE Select	c.522C>T	p.Cys174Cys	synonymous	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_001425155.1		c.522C>T	p.Cys174Cys	synonymous	Exon 2 of 3	NP_001412084.1
	SLC35C1	NM_001145265.2		c.483C>T	p.Cys161Cys	synonymous	Exon 2 of 3	NP_001138737.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.522C>T	p.Cys174Cys	synonymous	Exon 1 of 2	ENSP00000313318.3
	SLC35C1	ENST00000442528.2	TSL:1	c.483C>T	p.Cys161Cys	synonymous	Exon 2 of 3	ENSP00000412408.2
	SLC35C1	ENST00000526817.2	TSL:2	c.483C>T	p.Cys161Cys	synonymous	Exon 2 of 3	ENSP00000432145.2

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 415 AN: 152130 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00272 AC: 679 AN: 249702 AF XY: 0.00257

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.00230

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00267 AC: 3906 AN: 1460416 Hom.: 13 Cov.: 35 AF XY: 0.00259 AC XY: 1879 AN XY: 726524

African (AFR) AF: 0.000299 AC: 10 AN: 33480

American (AMR) AF: 0.00268 AC: 120 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

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

South Asian (SAS) AF: 0.000707 AC: 61 AN: 86246

European-Finnish (FIN) AF: 0.0129 AC: 670 AN: 52018

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00263 AC: 2928 AN: 1111982

Other (OTH) AF: 0.00187 AC: 113 AN: 60382

GnomAD4 genome AF: 0.00273 AC: 415 AN: 152248 Hom.: 1 Cov.: 32 AF XY: 0.00318 AC XY: 237 AN XY: 74454

African (AFR) AF: 0.000457 AC: 19 AN: 41544

American (AMR) AF: 0.00203 AC: 31 AN: 15296

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.0176 AC: 187 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00240 AC: 163 AN: 67998

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00160 Hom.: 0

Bravo AF: 0.00162

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00166

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	1	1	Leukocyte adhesion deficiency type II (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.2
DANN	Benign	0.58
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	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: rs141379070; hg19: chr11-45827874; COSMIC: COSV58479447; COSMIC: COSV58479447;