11-45805799-A-G

Position:

chr11-45805799-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000442528.2(SLC35C1):c.-31-11A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,612,660 control chromosomes in the GnomAD database, including 39,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6084 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33673 hom. )

Consequence

SLC35C1
ENST00000442528.2 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.745

Variant links:

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]

SLC35C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 11-45805799-A-G is Benign according to our data. Variant chr11-45805799-A-G is described in ClinVar as [Benign]. Clinvar id is 95903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SLC35C1	NM_018389.5 linkuse as main transcript	c.-3A>G	5_prime_UTR_variant	1/2	ENST00000314134.4	NP_060859.4
SLC35C1	XM_011520203.4 linkuse as main transcript	c.-3A>G	5_prime_UTR_variant	1/2		XP_011518505.1
SLC35C1	NM_001145265.2 linkuse as main transcript	c.-31-11A>G	splice_polypyrimidine_tract_variant, intron_variant			NP_001138737.1
SLC35C1	NM_001145266.1 linkuse as main transcript	c.-31-11A>G	splice_polypyrimidine_tract_variant, intron_variant			NP_001138738.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35C1	ENST00000314134.4 linkuse as main transcript	c.-3A>G	5_prime_UTR_variant	1/2	1	NM_018389.5	ENSP00000313318	P4	Q96A29-1
SLC35C1	ENST00000442528.2 linkuse as main transcript	c.-31-11A>G	splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000412408	A1	Q96A29-2
SLC35C1	ENST00000526817.2 linkuse as main transcript	c.-31-11A>G	splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000432145	A1	Q96A29-2
SLC35C1	ENST00000530471.1 linkuse as main transcript	c.-31-11A>G	splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000432669

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39871

AN:

152020

Hom.:

6070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.203

AC:

50541

AN:

249226

Hom.:

5889

AF XY:

0.198

AC XY:

26802

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.127

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.209

AC:

305644

AN:

1460522

Hom.:

33673

Cov.:

AF XY:

0.206

AC XY:

149905

AN XY:

726548

show subpopulations

Gnomad4 AFR exome

AF:

0.429

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.262

AC:

39928

AN:

152138

Hom.:

6084

Cov.:

AF XY:

0.260

AC XY:

19366

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.278

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.214

Hom.:

2863

Bravo

AF:

0.261

Asia WGS

AF:

0.155

AC:

540

AN:

3478

EpiCase

AF:

0.198

EpiControl

AF:

0.195

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 04, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Leukocyte adhesion deficiency type II

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over