16-67675874-T-A

Position:

• chr16-67675874-T-A

Variant summary

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

The NM_030819.4(GFOD2):​c.439A>T​(p.Ile147Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GFOD2 NM_030819.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41021964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFOD2	NM_030819.4	c.439A>T	p.Ile147Phe	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.439A>T	p.Ile147Phe	missense_variant	3/3	1	NM_030819.4	ENSP00000268797.7
GFOD2	ENST00000602377	c.*117A>T		3_prime_UTR_variant	3/3	4		ENSP00000477784.1
GFOD2	ENST00000602522.1	n.1611A>T		non_coding_transcript_exon_variant	1/1	6
GFOD2	ENST00000602627.1	c.*117A>T		downstream_gene_variant		3		ENSP00000483913.1

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 30, 2021

The c.439A>T (p.I147F) alteration is located in exon 3 (coding exon 2) of the GFOD2 gene. This alteration results from a A to T substitution at nucleotide position 439, causing the isoleucine (I) at amino acid position 147 to be replaced by a phenylalanine (F). 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	Pathogenic	0.73
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.016	D
Polyphen		0.18	B
Vest4		0.61
MutPred		0.56		Gain of catalytic residue at I147 (P = 0.0193);
MVP		0.32
MPC		0.93
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.45
gMVP		0.93

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: chr16-67709777;