1-18916957-T-A

Variant names:

• chr1-18916957-T-A
• rs751938671
• NM_001136265.2:c.1049A>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.1049A>T​(p.Asp350Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D350Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: IFFO2 NM_001136265.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• 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=0.40695405).

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.1049A>T	p.Asp350Val	missense	Exon 5 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.1049A>T	p.Asp350Val	missense	Exon 5 of 9	ENSP00000387941.2	Q5TF58
	IFFO2	ENST00000944819.1		c.1112A>T	p.Asp371Val	missense	Exon 6 of 10	ENSP00000614878.1
	IFFO2	ENST00000416166.1	TSL:3	c.272A>T	p.Asp91Val	missense	Exon 4 of 8	ENSP00000394655.1	H0Y4W3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000634 AC: 1 AN: 157762 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399710 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690358

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.0000560 AC: 2 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079036

Other (OTH) AF: 0.00 AC: 0 AN: 58084

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000383 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.066	T
Eigen	Benign	0.076
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.2	L
PhyloP100		8.0
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.46
Sift	Benign	0.040	D
Sift4G	Benign	0.12	T
Polyphen		0.88	P
Vest4		0.30
MutPred		0.46		Loss of solvent accessibility (P = 0.1579)
MVP		0.90
MPC		1.7
ClinPred		0.89	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.74
Mutation Taster		=53/47	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: rs751938671; hg19: chr1-19243451;