11-45810958-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I240L) has been classified as Uncertain significance.

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

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

leukocyte adhesion deficiency type II
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia

SLC35C1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 95905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35C1	NM_018389.5	MANE Select	c.718A>G	p.Ile240Val	missense	Exon 2 of 2	NP_060859.4
SLC35C1	NM_001425155.1		c.718A>G	p.Ile240Val	missense	Exon 3 of 3	NP_001412084.1	B3KQH0
SLC35C1	NM_001145265.2		c.679A>G	p.Ile227Val	missense	Exon 3 of 3	NP_001138737.1	Q96A29-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.718A>G	p.Ile240Val	missense	Exon 2 of 2	ENSP00000313318.3	Q96A29-1
SLC35C1	ENST00000442528.2	TSL:1	c.679A>G	p.Ile227Val	missense	Exon 3 of 3	ENSP00000412408.2	Q96A29-2
SLC35C1	ENST00000953729.1		c.718A>G	p.Ile240Val	missense	Exon 3 of 3	ENSP00000623788.1

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

GnomAD2 exomes

AF:

0.0916

AC:

22925

AN:

250400

AF XY:

0.0874

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 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

African (AFR)

AF:

0.208

AC:

6977

AN:

33480

American (AMR)

AF:

0.0608

AC:

2719

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0913

AC:

2386

AN:

26136

East Asian (EAS)

AF:

0.000428

AC:

AN:

39700

South Asian (SAS)

AF:

0.0242

AC:

2087

AN:

86258

European-Finnish (FIN)

AF:

0.122

AC:

6320

AN:

51986

Middle Eastern (MID)

AF:

0.0492

AC:

284

AN:

5768

European-Non Finnish (NFE)

AF:

0.114

AC:

126855

AN:

1111978

Other (OTH)

AF:

0.102

AC:

6177

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

9540

19081

28621

38162

47702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4550

9100

13650

18200

22750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.127

AC:

19337

AN:

152290

Hom.:

1487

Cov.:

AF XY:

0.125

AC XY:

9279

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.200

AC:

8304

AN:

41556

American (AMR)

AF:

0.0962

AC:

1472

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0974

AC:

338

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.0230

AC:

111

AN:

4834

European-Finnish (FIN)

AF:

0.110

AC:

1171

AN:

10614

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7630

AN:

68016

Other (OTH)

AF:

0.104

AC:

221

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

899

1797

2696

3594

4493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.110

Hom.:

3253

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Leukocyte adhesion deficiency type II (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.85

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.11

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.75

PhyloP100

0.59

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.13

REVEL

Benign

0.063

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.017

MPC

0.46

ClinPred

0.00030

GERP RS

1.1

Varity_R

0.031

gMVP

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over