16-67675450-C-A

Position:

• chr16-67675450-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030819.4(GFOD2):​c.863G>T​(p.Gly288Val) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GFOD2 NM_030819.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.367

Genes affected

GFOD2 (HGNC:28159): (Gfo/Idh/MocA-like oxidoreductase domain containing 2) Predicted to enable nucleotide binding activity and oxidoreductase activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

GFOD2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072402745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFOD2	NM_030819.4	c.863G>T	p.Gly288Val	missense_variant	3/3	ENST00000268797.12	NP_110446.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFOD2	ENST00000268797.12	c.863G>T	p.Gly288Val	missense_variant	3/3	1	NM_030819.4	ENSP00000268797.7
GFOD2	ENST00000602377	c.*541G>T		3_prime_UTR_variant	3/3	4		ENSP00000477784.1
GFOD2	ENST00000602522.1	n.2035G>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 10, 2024

The c.863G>T (p.G288V) alteration is located in exon 3 (coding exon 2) of the GFOD2 gene. This alteration results from a G to T substitution at nucleotide position 863, causing the glycine (G) at amino acid position 288 to be replaced by a valine (V). 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	0.095
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.0
DANN	Benign	0.60
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.010
Sift	Benign	0.22	T
Sift4G	Benign	0.36	T
Polyphen		0.022	B
Vest4		0.11
MutPred		0.32		Gain of helix (P = 0.0325);
MVP		0.42
MPC		0.39
ClinPred		0.049	T
GERP RS		1.8
Varity_R		0.037
gMVP		0.68

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: chr16-67709353;