chr11-45805889-G-A

Position:

chr11-45805889-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018389.5(SLC35C1):c.88G>A(p.Gly30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

SLC35C1
NM_018389.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.395

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054750085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35C1	NM_018389.5 linkuse as main transcript	c.88G>A	p.Gly30Arg	missense_variant	1/2	ENST00000314134.4	NP_060859.4	Q96A29-1B3KQH0
SLC35C1	NM_001145265.2 linkuse as main transcript	c.49G>A	p.Gly17Arg	missense_variant	2/3		NP_001138737.1	Q96A29-2
SLC35C1	NM_001145266.1 linkuse as main transcript	c.49G>A	p.Gly17Arg	missense_variant	2/3		NP_001138738.1	Q96A29-2
SLC35C1	XM_011520203.4 linkuse as main transcript	c.88G>A	p.Gly30Arg	missense_variant	1/2		XP_011518505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC35C1	ENST00000314134.4 linkuse as main transcript	c.88G>A	p.Gly30Arg	missense_variant	1/2	1	NM_018389.5	ENSP00000313318.3	Q96A29-1
SLC35C1	ENST00000442528.2 linkuse as main transcript	c.49G>A	p.Gly17Arg	missense_variant	2/3	1		ENSP00000412408.2	Q96A29-2
SLC35C1	ENST00000526817.2 linkuse as main transcript	c.49G>A	p.Gly17Arg	missense_variant	2/3	2		ENSP00000432145.2	Q96A29-2E9PS26
SLC35C1	ENST00000530471.1 linkuse as main transcript	c.49G>A	p.Gly17Arg	missense_variant	2/2	3		ENSP00000432669.1	E9PPI4

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251426

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000595

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000755

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.88G>A (p.G30R) alteration is located in exon 1 (coding exon 1) of the SLC35C1 gene. This alteration results from a G to A substitution at nucleotide position 88, causing the glycine (G) at amino acid position 30 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Leukocyte adhesion deficiency type II

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 14, 2022

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 30 of the SLC35C1 protein (p.Gly30Arg). This variant is present in population databases (rs761945760, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with SLC35C1-related conditions. ClinVar contains an entry for this variant (Variation ID: 566519). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.9

DANN

Uncertain

0.98

DEOGEN2

Benign

0.088

.;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.055

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.66

.;.;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.49

N;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.52

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.10

MutPred

0.32

.;.;Gain of solvent accessibility (P = 0.0097);.;

MVP

0.41

MPC

0.65

ClinPred

0.035

GERP RS

-1.2

Varity_R

0.023

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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