11-45811215-G-T

Variant names:

• chr11-45811215-G-T
• rs377098836
• NM_018389.5:c.975G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018389.5(SLC35C1):​c.975G>T​(p.Thr325Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T325T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC35C1 NM_018389.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.05
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-4.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018389.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	NM_018389.5	MANE Select	c.975G>T	p.Thr325Thr	synonymous	Exon 2 of 2	NP_060859.4
	SLC35C1	NM_001425155.1		c.975G>T	p.Thr325Thr	synonymous	Exon 3 of 3	NP_001412084.1
	SLC35C1	NM_001145265.2		c.936G>T	p.Thr312Thr	synonymous	Exon 3 of 3	NP_001138737.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.975G>T	p.Thr325Thr	synonymous	Exon 2 of 2	ENSP00000313318.3
	SLC35C1	ENST00000442528.2	TSL:1	c.936G>T	p.Thr312Thr	synonymous	Exon 3 of 3	ENSP00000412408.2
	SLC35C1	ENST00000953729.1		c.975G>T	p.Thr325Thr	synonymous	Exon 3 of 3	ENSP00000623788.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457126 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 724354

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109566

Other (OTH) AF: 0.00 AC: 0 AN: 60224

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.10
DANN	Benign	0.81
PhyloP100		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs377098836; hg19: chr11-45832766; COSMIC: COSV100029351; COSMIC: COSV100029351;