rs28937886

chr11-45811163-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_018389.5(SLC35C1):c.923C>G(p.Thr308Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. T308T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC35C1 NM_018389.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.67

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974
• PP5: Variant 11-45811163-C-G is Pathogenic according to our data. Variant chr11-45811163-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 4740.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-45811163-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35C1	NM_018389.5	c.923C>G	p.Thr308Arg	missense_variant	2/2	ENST00000314134.4
SLC35C1	NM_001145265.2	c.884C>G	p.Thr295Arg	missense_variant	3/3
SLC35C1	NM_001145266.1	c.884C>G	p.Thr295Arg	missense_variant	3/3
SLC35C1	XM_011520202.3	c.416C>G	p.Thr139Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35C1	ENST00000314134.4	c.923C>G	p.Thr308Arg	missense_variant	2/2	1	NM_018389.5	P4
SLC35C1	ENST00000442528.2	c.884C>G	p.Thr295Arg	missense_variant	3/3	1		A1
SLC35C1	ENST00000526817.2	c.884C>G	p.Thr295Arg	missense_variant	3/3	2		A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Leukocyte adhesion deficiency type II Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 15, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
Cadd	Pathogenic	31
Dann	Uncertain	0.99
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.080	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	0.18	D
MutationTaster	Benign	1.0	A;A;A
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	.;D
Vest4		0.97
MutPred		0.89		.;Gain of methylation at T308 (P = 0.0189);
MVP		0.94
MPC		1.6
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.98
gMVP		0.97

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

Other links and lift over

dbSNP: rs28937886; hg19: chr11-45832714;