1-201194249-C-G

Variant summary

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

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

Scores

3
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
IGFN1NM_001164586.2 linkc.103C>G p.Pro35Ala missense_variant Exon 3 of 24 ENST00000335211.9 NP_001158058.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGFN1ENST00000335211.9 linkc.103C>G p.Pro35Ala missense_variant Exon 3 of 24 5 NM_001164586.2 ENSP00000334714.4 Q86VF2-5
IGFN1ENST00000437879.6 linkn.103C>G non_coding_transcript_exon_variant Exon 3 of 26 1 ENSP00000399041.2 Q86VF2-4
IGFN1ENST00000295591.12 linkc.103C>G p.Pro35Ala missense_variant Exon 3 of 25 5 ENSP00000295591.9 Q86VF2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.000104
AC:
16
AN:
154494
Hom.:
0
AF XY:
0.0000610
AC XY:
5
AN XY:
81980
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000504
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
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.103C>G (p.P35A) alteration is located in exon 3 (coding exon 2) of the IGFN1 gene. This alteration results from a C to G substitution at nucleotide position 103, causing the proline (P) at amino acid position 35 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
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;T
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.72
D;D
MetaSVM
Benign
-0.30
T
MutationAssessor
Pathogenic
3.5
H;H
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-3.1
D;.
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Vest4
0.42
MutPred
0.78
Loss of disorder (P = 0.0707);Loss of disorder (P = 0.0707);
MVP
0.60
ClinPred
0.53
D
GERP RS
4.9
Varity_R
0.24
gMVP
0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1405374899; hg19: chr1-201163377; API