11-45811287-G-A

Position:

• chr11-45811287-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018389.5(SLC35C1):​c.1047G>A​(p.Pro349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000713 in 1,564,154 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (3 hom.)
• Consequence: SLC35C1 NM_018389.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.39

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 11-45811287-G-A is Benign according to our data. Variant chr11-45811287-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 390906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-45811287-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00367 (559/152356) while in subpopulation AFR AF= 0.0127 (530/41590). AF 95% confidence interval is 0.0118. There are 4 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35C1	NM_018389.5	c.1047G>A	p.Pro349=	synonymous_variant	2/2	ENST00000314134.4	NP_060859.4
SLC35C1	NM_001145265.2	c.1008G>A	p.Pro336=	synonymous_variant	3/3		NP_001138737.1
SLC35C1	NM_001145266.1	c.1008G>A	p.Pro336=	synonymous_variant	3/3		NP_001138738.1
SLC35C1	XM_011520202.3	c.540G>A	p.Pro180=	synonymous_variant	2/2		XP_011518504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35C1	ENST00000314134.4	c.1047G>A	p.Pro349=	synonymous_variant	2/2	1	NM_018389.5	ENSP00000313318	P4
SLC35C1	ENST00000442528.2	c.1008G>A	p.Pro336=	synonymous_variant	3/3	1		ENSP00000412408	A1
SLC35C1	ENST00000526817.2	c.1008G>A	p.Pro336=	synonymous_variant	3/3	2		ENSP00000432145	A1

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 554 AN: 152238 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000924 AC: 186 AN: 201380 Hom.: 0 AF XY: 0.000684 AC XY: 76 AN XY: 111056

Gnomad AFR exome AF: 0.0120

Gnomad AMR exome AF: 0.000413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000950

Gnomad OTH exome AF: 0.000207

GnomAD4 exome AF: 0.000395 AC: 557 AN: 1411798 Hom.: 3 Cov.: 36 AF XY: 0.000375 AC XY: 262 AN XY: 698440

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.000407

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000161

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000596

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.00367 AC: 559 AN: 152356 Hom.: 4 Cov.: 33 AF XY: 0.00334 AC XY: 249 AN XY: 74500

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00179 Hom.: 0

Bravo AF: 0.00424

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Leukocyte adhesion deficiency type II Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SLC35C1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.9
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs113735964; hg19: chr11-45832838;