19-5866758-T-C

Position:

• chr19-5866758-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002034.2(FUT5):​c.968A>G​(p.Asp323Gly) variant causes a missense 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FUT5 NM_002034.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2846681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT5	NM_002034.2	c.968A>G	p.Asp323Gly	missense_variant	2/2	ENST00000588525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT5	ENST00000588525.1	c.968A>G	p.Asp323Gly	missense_variant	2/2	1	NM_002034.2	P1
FUT5	ENST00000252675.6	c.968A>G	p.Asp323Gly	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000465 AC: 1 AN: 214830 Hom.: 0 AF XY: 0.00000852 AC XY: 1 AN XY: 117310

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000355

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.90e-7 AC: 1 AN: 1448662 Hom.: 0 Cov.: 55 AF XY: 0.00000139 AC XY: 1 AN XY: 720230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000834 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Uncertain	1.0
Eigen	Benign	-0.069
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.71	T;.
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	0.84	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.8	D;.
REVEL	Benign	0.10
Sift	Uncertain	0.0090	D;.
Sift4G	Benign	0.063	T;T
Vest4		0.23
MVP		0.69
MPC		1.6
ClinPred		0.80	D
GERP RS		2.3
gMVP		0.61

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: rs768406993; hg19: chr19-5866769; COSMIC: COSV99398833; COSMIC: COSV99398833;