NM_001136265.2:c.1523G>T

Variant names:

• chr1-18908592-C-A
• rs377002676
• NM_001136265.2:c.1523G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136265.2(IFFO2):​c.1523G>T​(p.Arg508Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R508C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IFFO2 NM_001136265.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29989505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136265.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFFO2	NM_001136265.2	MANE Select	c.1523G>T	p.Arg508Leu	missense	Exon 9 of 9	NP_001129737.1	Q5TF58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFFO2	ENST00000455833.7	TSL:5 MANE Select	c.1523G>T	p.Arg508Leu	missense	Exon 9 of 9	ENSP00000387941.2	Q5TF58
	IFFO2	ENST00000944819.1		c.1586G>T	p.Arg529Leu	missense	Exon 10 of 10	ENSP00000614878.1
	IFFO2	ENST00000416166.1	TSL:3	c.746G>T	p.Arg249Leu	missense	Exon 8 of 8	ENSP00000394655.1	H0Y4W3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399352 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 690190

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078880

Other (OTH) AF: 0.00 AC: 0 AN: 58026

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.059
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.44
Sift	Benign	0.17	T
Sift4G	Uncertain	0.039	D
Polyphen		0.45	B
Vest4		0.44
MutPred		0.21		Loss of solvent accessibility (P = 0.3646)
MVP		0.95
MPC		1.5
ClinPred		0.87	D
GERP RS		4.4
Varity_R		0.28
gMVP		0.27
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs377002676; hg19: chr1-19235086;