11-45805889-G-C

Position:

• chr11-45805889-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018389.5(SLC35C1):​c.88G>C​(p.Gly30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,852 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC35C1 NM_018389.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053129077).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35C1	ENST00000314134.4	c.88G>C	p.Gly30Arg	missense_variant	1/2	1	NM_018389.5	ENSP00000313318.3
SLC35C1	ENST00000442528.2	c.49G>C	p.Gly17Arg	missense_variant	2/3	1		ENSP00000412408.2
SLC35C1	ENST00000526817.2	c.49G>C	p.Gly17Arg	missense_variant	2/3	2		ENSP00000432145.2
SLC35C1	ENST00000530471.1	c.49G>C	p.Gly17Arg	missense_variant	2/2	3		ENSP00000432669.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251426 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135894

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: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461852 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.99
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	.;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.053	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.66	.;.;N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.49	N;N;N;N
REVEL	Benign	0.050
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		0.041	T
GERP RS		-1.2
Varity_R		0.023
gMVP		0.21

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: rs761945760; hg19: chr11-45827440;