NM_018389.5:c.-546_-540dupGAGCCCC

Variant names:

• chr11-45805249-A-AAGCCCCG
• rs886048308
• NM_018389.5:c.-546_-540dupGAGCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_018389.5(SLC35C1):​c.-546_-540dupGAGCCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000077 in 973,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: SLC35C1 NM_018389.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.00
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0000807 (68/843050) while in subpopulation NFE AF = 0.0000847 (65/766976). AF 95% confidence interval is 0.0000681. There are 0 homozygotes in GnomAdExome4. There are 32 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. 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.-546_-540dupGAGCCCC		5_prime_UTR	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_001425156.1		c.-92_-86dupGAGCCCC		5_prime_UTR	Exon 1 of 3	NP_001412085.1	Q96A29-2
	SLC35C1	NM_001425155.1		c.-219-327_-219-321dupGAGCCCC		intron	N/A	NP_001412084.1	B3KQH0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.-546_-540dupGAGCCCC		5_prime_UTR	Exon 1 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000442528.2	TSL:1	c.-31-554_-31-548dupGAGCCCC		intron	N/A	ENSP00000412408.2	Q96A29-2
	SLC35C1	ENST00000530471.1	TSL:3	c.-92_-86dupGAGCCCC		5_prime_UTR	Exon 1 of 2	ENSP00000432669.1	E9PPI4

Frequencies

GnomAD3 genomes AF: 0.0000535 AC: 7 AN: 130738 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000114

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000807 AC: 68 AN: 843050 Hom.: 0 Cov.: 30 AF XY: 0.0000820 AC XY: 32 AN XY: 390258

African (AFR) AF: 0.00 AC: 0 AN: 15918

American (AMR) AF: 0.00 AC: 0 AN: 2474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5256

East Asian (EAS) AF: 0.00 AC: 0 AN: 4296

South Asian (SAS) AF: 0.00 AC: 0 AN: 18294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1636

European-Non Finnish (NFE) AF: 0.0000847 AC: 65 AN: 766976

Other (OTH) AF: 0.000108 AC: 3 AN: 27712

GnomAD4 genome AF: 0.0000535 AC: 7 AN: 130738 Hom.: 0 Cov.: 32 AF XY: 0.0000633 AC XY: 4 AN XY: 63220

African (AFR) AF: 0.00 AC: 0 AN: 33486

American (AMR) AF: 0.00 AC: 0 AN: 12658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3170

East Asian (EAS) AF: 0.00 AC: 0 AN: 4618

South Asian (SAS) AF: 0.00 AC: 0 AN: 4338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000114 AC: 7 AN: 61568

Other (OTH) AF: 0.00 AC: 0 AN: 1744

Alfa AF: 0.0000712 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886048308; hg19: chr11-45826800;