1-201194249-C-G

Variant names:

• chr1-201194249-C-G
• rs1405374899
• NM_001164586.2:c.103C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001164586.2(IGFN1):​c.103C>G​(p.Pro35Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000129 in 1,399,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P35P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: IGFN1 NM_001164586.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

Genes affected

IGFN1 (HGNC:24607): (immunoglobulin like and fibronectin type III domain containing 1) Predicted to be involved in homophilic cell adhesion via plasma membrane adhesion molecules; retina layer formation; and synapse assembly. Predicted to be located in Z disc and nucleus. Predicted to be active in synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164586.2. 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
	IGFN1	NM_001164586.2	MANE Select	c.103C>G	p.Pro35Ala	missense	Exon 3 of 24	NP_001158058.1	Q86VF2-5
	IGFN1	NM_001367841.1		c.103C>G	p.Pro35Ala	missense	Exon 3 of 25	NP_001354770.1	Q86VF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFN1	ENST00000335211.9	TSL:5 MANE Select	c.103C>G	p.Pro35Ala	missense	Exon 3 of 24	ENSP00000334714.4	Q86VF2-5
	IGFN1	ENST00000437879.6	TSL:1	n.103C>G		non_coding_transcript_exon	Exon 3 of 26	ENSP00000399041.2	Q86VF2-4
	IGFN1	ENST00000295591.12	TSL:5	c.103C>G	p.Pro35Ala	missense	Exon 3 of 25	ENSP00000295591.9	Q86VF2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000104 AC: 16 AN: 154494 AF XY: 0.0000610

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000648

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: 0.0000129 AC: 18 AN: 1399276 Hom.: 0 Cov.: 31 AF XY: 0.00000580 AC XY: 4 AN XY: 690144

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.000504 AC: 18 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078906

Other (OTH) AF: 0.00 AC: 0 AN: 57986

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	Pathogenic	0.73
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		5.8
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.42
MutPred		0.78		Loss of disorder (P = 0.0707)
MVP		0.60
ClinPred		0.53	D
GERP RS		4.9
Varity_R		0.24
gMVP		0.24
Mutation Taster		=219/81	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: rs1405374899; hg19: chr1-201163377;