NM_001164586.2:c.305G>C

Variant names:

• chr1-201197255-G-C
• rs4915221
• NM_001164586.2:c.305G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001164586.2(IGFN1):​c.305G>C​(p.Arg102Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,980 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IGFN1 NM_001164586.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• Publications: 25 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 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
IGFN1	NM_001164586.2	c.305G>C	p.Arg102Pro	missense_variant	Exon 5 of 24	ENST00000335211.9	NP_001158058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFN1	ENST00000335211.9	c.305G>C	p.Arg102Pro	missense_variant	Exon 5 of 24	5	NM_001164586.2	ENSP00000334714.4
IGFN1	ENST00000437879.6	n.305G>C		non_coding_transcript_exon_variant	Exon 5 of 26	1		ENSP00000399041.2
IGFN1	ENST00000295591.12	c.305G>C	p.Arg102Pro	missense_variant	Exon 5 of 25	5		ENSP00000295591.9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398980 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 689964

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

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49236

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

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078626

Other (OTH) AF: 0.00 AC: 0 AN: 57996

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 118614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0	.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.5	H;H
PhyloP100		0.89
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.5	N;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0050	D;D
Vest4		0.53
ClinPred		0.53	D
GERP RS		3.2
Varity_R		0.74
gMVP		0.83
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs4915221; hg19: chr1-201166383;