chr11-45805169-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_018389.5(SLC35C1):​c.-633T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 990,510 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (6 hom.)
• Consequence: SLC35C1 NM_018389.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00179 (272/151792) while in subpopulation AMR AF = 0.00524 (80/15278). AF 95% confidence interval is 0.00431. There are 2 homozygotes in GnomAd4. There are 119 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	NM_018389.5	MANE Select	c.-633T>G		5_prime_UTR	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_001425156.1		c.-179T>G		5_prime_UTR	Exon 1 of 3	NP_001412085.1	Q96A29-2
	SLC35C1	NM_001425155.1		c.-219-414T>G		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>G		5_prime_UTR	Exon 1 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000442528.2	TSL:1	c.-31-641T>G		intron	N/A	ENSP00000412408.2	Q96A29-2
	SLC35C1	ENST00000530471.1	TSL:3	c.-179T>G		5_prime_UTR	Exon 1 of 2	ENSP00000432669.1	E9PPI4

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 272 AN: 151676 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00217

Gnomad OTH AF: 0.00288

GnomAD4 exome AF: 0.00274 AC: 2296 AN: 838718 Hom.: 6 Cov.: 30 AF XY: 0.00274 AC XY: 1064 AN XY: 387808

African (AFR) AF: 0.000190 AC: 3 AN: 15804

American (AMR) AF: 0.00477 AC: 10 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: 0.00202 AC: 35 AN: 17364

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

Middle Eastern (MID) AF: 0.00184 AC: 3 AN: 1632

European-Non Finnish (NFE) AF: 0.00287 AC: 2199 AN: 764942

Other (OTH) AF: 0.00167 AC: 46 AN: 27540

GnomAD4 genome AF: 0.00179 AC: 272 AN: 151792 Hom.: 2 Cov.: 33 AF XY: 0.00160 AC XY: 119 AN XY: 74192

African (AFR) AF: 0.000797 AC: 33 AN: 41392

American (AMR) AF: 0.00524 AC: 80 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4804

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00217 AC: 147 AN: 67820

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.00250 Hom.: 0

Bravo AF: 0.00226

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	0.037
DANN	Benign	0.71
PhyloP100		-6.7
PromoterAI		0.022	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: rs566857902; hg19: chr11-45826720;