14-65616075-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001371533.1(FUT8):c.301A>C(p.Lys101Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0134 in 1,613,820 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (47 hom., cov: 32)
  • Exomes 𝑓: 0.013 (242 hom.)
• Consequence: FUT8 NM_001371533.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.79

Genes affected

FUT8 (HGNC:4019): (fucosyltransferase 8) This gene encodes an enzyme belonging to the family of fucosyltransferases. The product of this gene catalyzes the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides. This enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition. The expression of this gene may contribute to the malignancy of cancer cells and to their invasive and metastatic capabilities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038077533).
• BP6: Variant 14-65616075-A-C is Benign according to our data. Variant chr14-65616075-A-C is described in ClinVar as [Benign]. Clinvar id is 1273382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0146 (2230/152338) while in subpopulation NFE AF= 0.0159 (1081/68024). AF 95% confidence interval is 0.0151. There are 47 homozygotes in gnomad4. There are 1303 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT8	NM_001371533.1	c.301A>C	p.Lys101Gln	missense_variant	4/11	ENST00000673929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT8	ENST00000673929.1	c.301A>C	p.Lys101Gln	missense_variant	4/11		NM_001371533.1	P1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2230 AN: 152220 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.0145 AC: 3625 AN: 250810 Hom.: 79 AF XY: 0.0147 AC XY: 1987 AN XY: 135566

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00669

Gnomad ASJ exome AF: 0.00973

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00150

Gnomad FIN exome AF: 0.0718

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0139

GnomAD4 exome AF: 0.0132 AC: 19318 AN: 1461482 Hom.: 242 Cov.: 30 AF XY: 0.0128 AC XY: 9323 AN XY: 727036

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.00653

Gnomad4 ASJ exome AF: 0.00945

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.0667

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.0146 AC: 2230 AN: 152338 Hom.: 47 Cov.: 32 AF XY: 0.0175 AC XY: 1303 AN XY: 74490

Gnomad4 AFR AF: 0.00257

Gnomad4 AMR AF: 0.00888

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0775

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0124 Hom.: 20

Bravo AF: 0.00890

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.0122 AC: 47

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0135 AC: 116

ExAC AF: 0.0127 AC: 1546

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0173

EpiControl AF: 0.0150

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 08, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	FUT8: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	21
Dann	Benign	0.97
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.098
Sift	Benign	0.32	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.019	B;B
Vest4		0.21
MPC		0.64
ClinPred		0.023	T
GERP RS		6.0
Varity_R		0.082
gMVP		0.18

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

Other links and lift over

dbSNP: rs2229678; hg19: chr14-66082793;