rs113735964

Variant names:

• chr11-45811287-G-A
• rs113735964
• NM_018389.5:c.1047G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018389.5(SLC35C1):​c.1047G>A​(p.Pro349Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000713 in 1,564,154 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (3 hom.)
• Consequence: SLC35C1 NM_018389.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.39
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 11-45811287-G-A is Benign according to our data. Variant chr11-45811287-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 390906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00367 (559/152356) while in subpopulation AFR AF = 0.0127 (530/41590). AF 95% confidence interval is 0.0118. There are 4 homozygotes in GnomAd4. There are 249 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	NM_018389.5	MANE Select	c.1047G>A	p.Pro349Pro	synonymous	Exon 2 of 2	NP_060859.4
	SLC35C1	NM_001425155.1		c.1047G>A	p.Pro349Pro	synonymous	Exon 3 of 3	NP_001412084.1	B3KQH0
	SLC35C1	NM_001145265.2		c.1008G>A	p.Pro336Pro	synonymous	Exon 3 of 3	NP_001138737.1	Q96A29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.1047G>A	p.Pro349Pro	synonymous	Exon 2 of 2	ENSP00000313318.3	Q96A29-1
	SLC35C1	ENST00000442528.2	TSL:1	c.1008G>A	p.Pro336Pro	synonymous	Exon 3 of 3	ENSP00000412408.2	Q96A29-2
	SLC35C1	ENST00000953729.1		c.1047G>A	p.Pro349Pro	synonymous	Exon 3 of 3	ENSP00000623788.1

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 554 AN: 152238 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000924 AC: 186 AN: 201380 AF XY: 0.000684

Gnomad AFR exome AF: 0.0120

Gnomad AMR exome AF: 0.000413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000950

Gnomad OTH exome AF: 0.000207

GnomAD4 exome AF: 0.000395 AC: 557 AN: 1411798 Hom.: 3 Cov.: 36 AF XY: 0.000375 AC XY: 262 AN XY: 698440

African (AFR) AF: 0.0125 AC: 401 AN: 32064

American (AMR) AF: 0.000407 AC: 16 AN: 39274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23708

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39166

South Asian (SAS) AF: 0.000161 AC: 13 AN: 80972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41912

Middle Eastern (MID) AF: 0.000397 AC: 2 AN: 5040

European-Non Finnish (NFE) AF: 0.0000596 AC: 65 AN: 1091452

Other (OTH) AF: 0.00101 AC: 59 AN: 58210

GnomAD4 genome AF: 0.00367 AC: 559 AN: 152356 Hom.: 4 Cov.: 33 AF XY: 0.00334 AC XY: 249 AN XY: 74500

African (AFR) AF: 0.0127 AC: 530 AN: 41590

American (AMR) AF: 0.00118 AC: 18 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00195 Hom.: 0

Bravo AF: 0.00424

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leukocyte adhesion deficiency type II (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.9
DANN	Benign	0.69
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

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: rs113735964; hg19: chr11-45832838; COSMIC: COSV106441450; COSMIC: COSV106441450;