chr8-33389004-C-A

Position:

• chr8-33389004-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032664.3(FUT10):​c.1171G>T​(p.Val391Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FUT10 NM_032664.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT10	NM_032664.3	c.1171G>T	p.Val391Leu	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.1171G>T	p.Val391Leu	missense_variant	4/5	1	NM_032664.3	ENSP00000332757	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Feb 28, 2023

The c.1171G>T (p.V391L) alteration is located in exon 4 (coding exon 3) of the FUT10 gene. This alteration results from a G to T substitution at nucleotide position 1171, causing the valine (V) at amino acid position 391 to be replaced by a leucine (L). 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	0.47
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D;D;D
Sift4G	Benign	0.062	T;T;T
Polyphen		0.94	P;.;.
Vest4		0.70
MutPred		0.68		Gain of loop (P = 0.069);.;.;
MVP		0.37
MPC		0.14
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.51
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs757366908; hg19: chr8-33246522; COSMIC: COSV59452927;