rs369993212

Variant names:

• chr9-137030858-C-T
• rs369993212
• NM_004479.4:c.881G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004479.4(FUT7):​c.881G>A​(p.Arg294Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,612,798 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: FUT7 NM_004479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.933
• Publications: 0 publications found

Genes affected

FUT7 (HGNC:4018): (fucosyltransferase 7) The protein encoded by this gene is a Golgi stack membrane protein that is involved in the creation of sialyl-Lewis X antigens. The encoded protein can direct the synthesis of the E-selectin-binding sialyl-Lewis X moiety. [provided by RefSeq, Jul 2008]

LINC02908 (HGNC:31426): (long intergenic non-protein coding RNA 2908)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09016365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT7	NM_004479.4	c.881G>A	p.Arg294Gln	missense_variant	Exon 2 of 2	ENST00000314412.7	NP_004470.1
LINC02908	NR_171031.1	n.449-1140C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT7	ENST00000314412.7	c.881G>A	p.Arg294Gln	missense_variant	Exon 2 of 2	1	NM_004479.4	ENSP00000318142.6
LINC02908	ENST00000623196.1	n.449-1140C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 249682 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1460436 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726504

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111954

Other (OTH) AF: 0.0000497 AC: 3 AN: 60378

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152362 Hom.: 1 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74510

African (AFR) AF: 0.0000962 AC: 4 AN: 41586

American (AMR) AF: 0.000261 AC: 4 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.881G>A (p.R294Q) alteration is located in exon 2 (coding exon 2) of the FUT7 gene. This alteration results from a G to A substitution at nucleotide position 881, causing the arginine (R) at amino acid position 294 to be replaced by a glutamine (Q). 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	Benign	0.074
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.7
DANN	Benign	0.93
DEOGEN2	Benign	0.099	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.93
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.028
Sift	Benign	0.41	T
Sift4G	Benign	0.40	T
Polyphen		0.060	B
Vest4		0.080
MVP		0.45
MPC		0.37
ClinPred		0.026	T
GERP RS		-2.0
Varity_R		0.045
gMVP		0.36
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs369993212; hg19: chr9-139925310; COSMIC: COSV99686726; COSMIC: COSV99686726;