8-33389418-G-C

Position:

• chr8-33389418-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032664.3(FUT10):​c.757C>G​(p.Pro253Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FUT10 NM_032664.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.99

Genes affected

FUT10 (HGNC:19234): (fucosyltransferase 10) Predicted to enable alpha-(1->3)-fucosyltransferase activity. Predicted to be involved in fucosylation. Predicted to act upstream of or within cerebral cortex radially oriented cell migration and neuronal stem cell population maintenance. Located in Golgi apparatus; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FUT10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT10	NM_032664.3	c.757C>G	p.Pro253Ala	missense_variant	4/5	ENST00000327671.10	NP_116053.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT10	ENST00000327671.10	c.757C>G	p.Pro253Ala	missense_variant	4/5	1	NM_032664.3	ENSP00000332757.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461878 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

The c.757C>G (p.P253A) alteration is located in exon 4 (coding exon 3) of the FUT10 gene. This alteration results from a C to G substitution at nucleotide position 757, causing the proline (P) at amino acid position 253 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-7.4	D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.032	D;D;D
Sift4G	Uncertain	0.042	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.86
MutPred		0.46		Loss of ubiquitination at K250 (P = 0.063);.;.;
MVP		0.55
MPC		0.21
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.71
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-33246936;