Genetic Variant SLC35C1:p.Pro352Thr (chr11-45811294-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018389.5(SLC35C1):c.1054C>A(p.Pro352Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P352S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SLC35C1
NM_018389.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

SLC35C1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09130427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35C1	NM_018389.5 link	c.1054C>A	p.Pro352Thr	missense_variant	Exon 2 of 2	ENST00000314134.4	NP_060859.4	Q96A29-1B3KQH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC35C1	ENST00000314134.4 link	c.1054C>A	p.Pro352Thr	missense_variant	Exon 2 of 2	1	NM_018389.5	ENSP00000313318.3	Q96A29-1
SLC35C1	ENST00000442528.2 link	c.1015C>A	p.Pro339Thr	missense_variant	Exon 3 of 3	1		ENSP00000412408.2	Q96A29-2
SLC35C1	ENST00000526817.2 link	c.1015C>A	p.Pro339Thr	missense_variant	Exon 3 of 3	2		ENSP00000432145.2	Q96A29-2E9PS26

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1404180

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31748

American (AMR)

AF:

0.00

AC:

AN:

37820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23196

East Asian (EAS)

AF:

0.00

AC:

AN:

39182

South Asian (SAS)

AF:

0.00

AC:

AN:

79504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4808

European-Non Finnish (NFE)

AF:

9.18e-7

AC:

AN:

1089498

Other (OTH)

AF:

0.00

AC:

AN:

57936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.085

.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.075

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.93

.;L

PhyloP100

1.5

PrimateAI

Benign

0.34

PROVEAN

Benign

0.90

N;N

REVEL

Benign

0.044

Sift

Benign

0.33

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0

.;B

Vest4

0.13

MutPred

0.28

.;Gain of phosphorylation at P352 (P = 0.0073);

MVP

0.78

MPC

0.62

ClinPred

0.20

GERP RS

4.8

Varity_R

0.087

gMVP

0.56

Mutation Taster

=89/11

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over