11-45810796-G-T

Variant names:

• chr11-45810796-G-T
• NM_018389.5:c.556G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018389.5(SLC35C1):​c.556G>T​(p.Asp186Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC35C1 NM_018389.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.70

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35C1	NM_018389.5	c.556G>T	p.Asp186Tyr	missense_variant	Exon 2 of 2	ENST00000314134.4	NP_060859.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35C1	ENST00000314134.4	c.556G>T	p.Asp186Tyr	missense_variant	Exon 2 of 2	1	NM_018389.5	ENSP00000313318.3
SLC35C1	ENST00000442528.2	c.517G>T	p.Asp173Tyr	missense_variant	Exon 3 of 3	1		ENSP00000412408.2
SLC35C1	ENST00000526817.2	c.517G>T	p.Asp173Tyr	missense_variant	Exon 3 of 3	2		ENSP00000432145.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460366 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 726576

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.98	.;D
Vest4		0.93
MutPred		0.70		.;Loss of disorder (P = 0.0405);
MVP		0.90
MPC		0.81
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.91
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-45832347;