ENST00000314134:c.-633T>C

Variant names:

• chr11-45805169-T-C
• rs566857902
• NM_018389.5:c.-633T>C

Variant summary

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

The ENST00000314134.4(SLC35C1):​c.-633T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000119 in 838,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: SLC35C1 ENST00000314134.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.70
• 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=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000314134.4. 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.-633T>C		5_prime_UTR	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_001425156.1		c.-179T>C		5_prime_UTR	Exon 1 of 3	NP_001412085.1	Q96A29-2
	SLC35C1	NM_001425155.1		c.-219-414T>C		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.-633T>C		5_prime_UTR	Exon 1 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000442528.2	TSL:1	c.-31-641T>C		intron	N/A	ENSP00000412408.2	Q96A29-2
	SLC35C1	ENST00000530471.1	TSL:3	c.-179T>C		5_prime_UTR	Exon 1 of 2	ENSP00000432669.1	E9PPI4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000119 AC: 1 AN: 838718 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 387808

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

African (AFR) AF: 0.00 AC: 0 AN: 15804

American (AMR) AF: 0.00 AC: 0 AN: 2096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5184

East Asian (EAS) AF: 0.00 AC: 0 AN: 3764

South Asian (SAS) AF: 0.00 AC: 0 AN: 17364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1632

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 764942

Other (OTH) AF: 0.00 AC: 0 AN: 27540

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.041
DANN	Benign	0.66
PhyloP100		-6.7
PromoterAI		0.062	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: rs566857902; hg19: chr11-45826720;