chr16-70463678-C-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_145059.3(FCSK):​c.138C>A​(p.Ala46Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 1,613,114 control chromosomes in the GnomAD database, including 842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 443 hom., cov: 32)
Exomes 𝑓: 0.0040 ( 399 hom. )

Consequence

FCSK
NM_145059.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.41
Variant links:
Genes affected
FCSK (HGNC:29500): (fucose kinase) The protein encoded by this gene belongs to the GHMP (galacto-, homoserine, mevalonate and phosphomevalonate) kinase family and catalyzes the phosphorylation of L-fucose to form beta-L-fucose 1-phosphate. This enzyme catalyzes the first step in the utilization of free L-fucose in glycoprotein and glycolipid synthesis. L-fucose may be important in mediating a number of cell-cell interactions such as blood group antigen recognition, inflammation, and metastatis. While several transcript variants may exist for this gene, the full-length nature of only one has been described to date. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 16-70463678-C-A is Benign according to our data. Variant chr16-70463678-C-A is described in ClinVar as [Benign]. Clinvar id is 1682342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.41 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FCSKNM_145059.3 linkc.138C>A p.Ala46Ala synonymous_variant Exon 3 of 24 ENST00000288078.11 NP_659496.2 Q8N0W3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FCSKENST00000288078.11 linkc.138C>A p.Ala46Ala synonymous_variant Exon 3 of 24 1 NM_145059.3 ENSP00000288078.6 Q8N0W3-1

Frequencies

GnomAD3 genomes
AF:
0.0404
AC:
6140
AN:
151986
Hom.:
436
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.140
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0170
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.0297
GnomAD3 exomes
AF:
0.0101
AC:
2502
AN:
248896
Hom.:
177
AF XY:
0.00768
AC XY:
1039
AN XY:
135232
show subpopulations
Gnomad AFR exome
AF:
0.145
Gnomad AMR exome
AF:
0.00658
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000160
Gnomad OTH exome
AF:
0.00265
GnomAD4 exome
AF:
0.00402
AC:
5879
AN:
1461010
Hom.:
399
Cov.:
31
AF XY:
0.00342
AC XY:
2485
AN XY:
726800
show subpopulations
Gnomad4 AFR exome
AF:
0.144
Gnomad4 AMR exome
AF:
0.00745
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000359
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000104
Gnomad4 OTH exome
AF:
0.00911
GnomAD4 genome
AF:
0.0405
AC:
6166
AN:
152104
Hom.:
443
Cov.:
32
AF XY:
0.0392
AC XY:
2913
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.141
Gnomad4 AMR
AF:
0.0170
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.0294
Alfa
AF:
0.0119
Hom.:
48
Bravo
AF:
0.0458
Asia WGS
AF:
0.00895
AC:
31
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jan 27, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

FCSK-related disorder Benign:1
Mar 26, 2024
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.076
DANN
Benign
0.48
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs60470914; hg19: chr16-70497581; API