Genetic Variant SLC35C1:c.-32+628C>A (chr11-45805145-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_001425155.1(SLC35C1):c.-219-438C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 986,380 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

SLC35C1
NM_001425155.1 intron

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -3.21

Publications

0 publications found

Variant links:

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 links:

LINC02690 (HGNC:54194): (long intergenic non-protein coding RNA 2690)

LINC02690 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000743 (113/152066) while in subpopulation AFR AF = 0.00246 (102/41488). AF 95% confidence interval is 0.00207. There are 0 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425155.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC35C1	NM_001425155.1	c.-219-438C>A	intron	N/A	NP_001412084.1	B3KQH0
SLC35C1	NM_001145265.2	c.-32+628C>A	intron	N/A	NP_001138737.1	Q96A29-2
SLC35C1	NM_001145266.2	c.-31-665C>A	intron	N/A	NP_001138738.1	Q96A29-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC35C1	ENST00000442528.2	TSL:1	c.-32+628C>A	intron	N/A	ENSP00000412408.2	Q96A29-2
SLC35C1	ENST00000953729.1		c.-219-438C>A	intron	N/A	ENSP00000623788.1
SLC35C1	ENST00000526817.2	TSL:2	c.-31-665C>A	intron	N/A	ENSP00000432145.2	Q96A29-2

Frequencies

GnomAD3 genomes

AF:

0.000750

AC:

114

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.0000479

AC:

AN:

834314

Hom.:

Cov.:

AF XY:

0.0000467

AC XY:

AN XY:

385404

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

15788

American (AMR)

AF:

0.000882

AC:

AN:

1134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5158

East Asian (EAS)

AF:

0.00

AC:

AN:

3638

South Asian (SAS)

AF:

0.00

AC:

AN:

16706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

296

Middle Eastern (MID)

AF:

0.000615

AC:

AN:

1626

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

762626

Other (OTH)

AF:

0.0000731

AC:

AN:

27342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000743

AC:

113

AN:

152066

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00246

AC:

102

AN:

41488

American (AMR)

AF:

0.000327

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67908

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.000722

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Leukocyte adhesion deficiency type II (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.2

(source)

DANN

Benign

0.55

PhyloP100

-3.2

PromoterAI

0.35

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over