chr19-5866966-A-G

Position:

• chr19-5866966-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002034.2(FUT5):​c.760T>C​(p.Tyr254His) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: FUT5 NM_002034.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.67

Genes affected

FUT5 (HGNC:4016): (fucosyltransferase 5) Enables 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity and 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity. Involved in ceramide metabolic process and oligosaccharide metabolic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT5	NM_002034.2	c.760T>C	p.Tyr254His	missense_variant	2/2	ENST00000588525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT5	ENST00000588525.1	c.760T>C	p.Tyr254His	missense_variant	2/2	1	NM_002034.2	P1
FUT5	ENST00000252675.6	c.760T>C	p.Tyr254His	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151620 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461604 Hom.: 0 Cov.: 92 AF XY: 0.00000413 AC XY: 3 AN XY: 727118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151620 Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1 AN XY: 74024

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;.
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.27	T
MutationTaster	Benign	0.89	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.0020	D;D
Vest4		0.56
MutPred		0.95		Loss of stability (P = 0.0126);Loss of stability (P = 0.0126);
MVP		0.82
MPC		1.7
ClinPred		0.99	D
GERP RS		2.1
gMVP		0.73

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: rs1325767392; hg19: chr19-5866977;