chr16-70471456-T-A

Variant names:

• chr16-70471456-T-A
• rs11861805
• NM_145059.3:c.1341+104T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145059.3(FCSK):​c.1341+104T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCSK NM_145059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 5 publications found

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]

FCSK Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation with defective fucosylation 2

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCSK	NM_145059.3	c.1341+104T>A		intron_variant	Intron 13 of 23	ENST00000288078.11	NP_659496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCSK	ENST00000288078.11	c.1341+104T>A		intron_variant	Intron 13 of 23	1	NM_145059.3	ENSP00000288078.6
FCSK	ENST00000378912.6	c.1437+104T>A		intron_variant	Intron 13 of 23	2		ENSP00000368192.2
FCSK	ENST00000571514.5	c.-208+104T>A		intron_variant	Intron 5 of 15	2		ENSP00000462584.1
FCSK	ENST00000464499.5	n.1646+104T>A		intron_variant	Intron 11 of 21	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1045066 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 514440

African (AFR) AF: 0.00 AC: 0 AN: 24052

American (AMR) AF: 0.00 AC: 0 AN: 22766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17772

East Asian (EAS) AF: 0.00 AC: 0 AN: 33454

South Asian (SAS) AF: 0.00 AC: 0 AN: 60132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4456

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 803104

Other (OTH) AF: 0.00 AC: 0 AN: 45548

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.22
DANN	Benign	0.46
PhyloP100		-0.58

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: rs11861805; hg19: chr16-70505359;