1-18910354-C-G

Variant names:

• chr1-18910354-C-G
• NM_001136265.2:c.1436G>C

Variant summary

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

The NM_001136265.2(IFFO2):​c.1436G>C​(p.Gly479Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IFFO2 NM_001136265.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34

Genes affected

IFFO2 (HGNC:27006): (intermediate filament family orphan 2) Predicted to be located in intermediate filament. [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 rank	MANE	Protein	UniProt
IFFO2	NM_001136265.2	c.1436G>C	p.Gly479Ala	missense_variant	Exon 8 of 9	ENST00000455833.7	NP_001129737.1
IFFO2	XM_011540630.3	c.1295G>C	p.Gly432Ala	missense_variant	Exon 7 of 8		XP_011538932.1
IFFO2	XM_047444839.1	c.1199G>C	p.Gly400Ala	missense_variant	Exon 6 of 7		XP_047300795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFFO2	ENST00000455833.7	c.1436G>C	p.Gly479Ala	missense_variant	Exon 8 of 9	5	NM_001136265.2	ENSP00000387941.2
IFFO2	ENST00000416166.1	c.659G>C	p.Gly220Ala	missense_variant	Exon 7 of 8	3		ENSP00000394655.1
IFFO2	ENST00000355609.8	c.149G>C	p.Gly50Ala	missense_variant	Exon 2 of 3	5		ENSP00000347820.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458644 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725234

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

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

Oct 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1436G>C (p.G479A) alteration is located in exon 8 (coding exon 8) of the IFFO2 gene. This alteration results from a G to C substitution at nucleotide position 1436, causing the glycine (G) at amino acid position 479 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	0.35
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.011	D;T
Sift4G	Benign	0.19	T;T
Polyphen		0.66	P;.
Vest4		0.55
MutPred		0.62		Loss of ubiquitination at K478 (P = 0.0675);.;
MVP		0.96
MPC		1.5
ClinPred		0.94	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.66

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: chr1-19236848;