NM_018389.5:c.-569C>T

Variant names:

• chr11-45805233-C-T
• rs886048307
• NM_018389.5:c.-569C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_018389.5(SLC35C1):​c.-569C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 995,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: SLC35C1 NM_018389.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.27
• 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]

LINC02690 (HGNC:54194): (long intergenic non-protein coding RNA 2690)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000132 (20/152042) while in subpopulation NFE AF = 0.000235 (16/67950). AF 95% confidence interval is 0.000147. There are 0 homozygotes in GnomAd4. There are 11 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.-569C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_018389.5	MANE Select	c.-569C>T		5_prime_UTR	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_001425156.1		c.-115C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001412085.1	Q96A29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.-569C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.-569C>T		5_prime_UTR	Exon 1 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000442528.2	TSL:1	c.-31-577C>T		intron	N/A	ENSP00000412408.2	Q96A29-2

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000664 AC: 56 AN: 843726 Hom.: 0 Cov.: 30 AF XY: 0.0000461 AC XY: 18 AN XY: 390506

African (AFR) AF: 0.00 AC: 0 AN: 15856

American (AMR) AF: 0.00 AC: 0 AN: 2908

Ashkenazi Jewish (ASJ) AF: 0.000764 AC: 4 AN: 5234

East Asian (EAS) AF: 0.00 AC: 0 AN: 4040

South Asian (SAS) AF: 0.00 AC: 0 AN: 18372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1644

European-Non Finnish (NFE) AF: 0.0000625 AC: 48 AN: 767426

Other (OTH) AF: 0.000144 AC: 4 AN: 27770

GnomAD4 genome AF: 0.000132 AC: 20 AN: 152042 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74262

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000869

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	4.7
DANN	Benign	0.91
PhyloP100		-2.3
PromoterAI		0.0091	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs886048307; hg19: chr11-45826784;