chr11-45810958-A-G

Position:

chr11-45810958-A-G

Variant summary

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

The NM_018389.5(SLC35C1):c.718A>G(p.Ile240Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,612,700 control chromosomes in the GnomAD database, including 10,560 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1487 hom., cov: 34)

Exomes 𝑓: 0.11 ( 9073 hom. )

Consequence

SLC35C1
NM_018389.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.592

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 (MetaRNN=0.0012888312).

BP6

Variant 11-45810958-A-G is Benign according to our data. Variant chr11-45810958-A-G is described in ClinVar as [Benign]. Clinvar id is 95905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-45810958-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC35C1	NM_018389.5 linkuse as main transcript	c.718A>G	p.Ile240Val	missense_variant	2/2	ENST00000314134.4	NP_060859.4
SLC35C1	NM_001145265.2 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	3/3		NP_001138737.1
SLC35C1	NM_001145266.1 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	3/3		NP_001138738.1
SLC35C1	XM_011520202.3 linkuse as main transcript	c.211A>G	p.Ile71Val	missense_variant	2/2		XP_011518504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35C1	ENST00000314134.4 linkuse as main transcript	c.718A>G	p.Ile240Val	missense_variant	2/2	1	NM_018389.5	ENSP00000313318	P4	Q96A29-1
SLC35C1	ENST00000442528.2 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	3/3	1		ENSP00000412408	A1	Q96A29-2
SLC35C1	ENST00000526817.2 linkuse as main transcript	c.679A>G	p.Ile227Val	missense_variant	3/3	2		ENSP00000432145	A1	Q96A29-2

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19325

AN:

152172

Hom.:

1488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.0826

Gnomad AMR

AF:

0.0965

Gnomad ASJ

AF:

0.0974

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.0916

AC:

22925

AN:

250400

Hom.:

1401

AF XY:

0.0874

AC XY:

11852

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.0591

Gnomad ASJ exome

AF:

0.0907

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0232

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.0953

GnomAD4 exome

AF:

0.105

AC:

153822

AN:

1460410

Hom.:

9073

Cov.:

AF XY:

0.102

AC XY:

74233

AN XY:

726578

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.0608

Gnomad4 ASJ exome

AF:

0.0913

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.0242

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.127

AC:

19337

AN:

152290

Hom.:

1487

Cov.:

AF XY:

0.125

AC XY:

9279

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.0962

Gnomad4 ASJ

AF:

0.0974

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.103

Hom.:

1965

Bravo

AF:

0.130

TwinsUK

AF:

0.122

AC:

454

ALSPAC

AF:

0.118

AC:

454

ESP6500AA

AF:

0.206

AC:

906

ESP6500EA

AF:

0.112

AC:

959

ExAC

AF:

0.0941

AC:

11426

EpiCase

AF:

0.108

EpiControl

AF:

0.102

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	Eurofins Ntd Llc (ga)	Oct 04, 2012	- -
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. -

Leukocyte adhesion deficiency type II

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.85

DANN

Benign

0.50

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.62

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.75

.;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.017

MPC

0.46

ClinPred

0.00030

GERP RS

1.1

Varity_R

0.031

gMVP

0.32

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

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