rs886048311

Variant names:

• chr11-45805409-C-T
• rs886048311
• NM_018389.5:c.-393C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-45805409-C-T
• chr11-45805409-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018389.5(SLC35C1):​c.-393C>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 0.00000668 in 149,660 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 0.0000067 (0 hom., cov: 30)
• Consequence: SLC35C1 NM_018389.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.-393C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_018389.5	MANE Select	c.-393C>T		5_prime_UTR	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_001425155.1		c.-219-174C>T		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.-393C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.-393C>T		5_prime_UTR	Exon 1 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000442528.2	TSL:1	c.-31-401C>T		intron	N/A	ENSP00000412408.2	Q96A29-2

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149660 Hom.: 0 Cov.: 30

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: 0.0000987

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149660 Hom.: 0 Cov.: 30 AF XY: 0.0000137 AC XY: 1 AN XY: 73088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40912

American (AMR) AF: 0.00 AC: 0 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 4878

South Asian (SAS) AF: 0.00 AC: 0 AN: 4606

European-Finnish (FIN) AF: 0.0000987 AC: 1 AN: 10132

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67330

Other (OTH) AF: 0.00 AC: 0 AN: 2068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	-0.83
CADD	Benign	1.1
DANN	Benign	0.85
PhyloP100		-1.2
PromoterAI		-0.12	Neutral

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: rs886048311; hg19: chr11-45826960;