chr1-201194177-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164586.2(IGFN1):​c.31C>T​(p.Pro11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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. P11R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

IGFN1
NM_001164586.2 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22607139).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IGFN1NM_001164586.2 linkc.31C>T p.Pro11Ser 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.31C>T p.Pro11Ser missense_variant Exon 3 of 24 5 NM_001164586.2 ENSP00000334714.4 Q86VF2-5
IGFN1ENST00000437879.6 linkn.31C>T non_coding_transcript_exon_variant Exon 3 of 26 1 ENSP00000399041.2 Q86VF2-4
IGFN1ENST00000295591.12 linkc.31C>T p.Pro11Ser missense_variant Exon 3 of 25 5 ENSP00000295591.9 Q86VF2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.31C>T (p.P11S) alteration is located in exon 3 (coding exon 2) of the IGFN1 gene. This alteration results from a C to T substitution at nucleotide position 31, causing the proline (P) at amino acid position 11 to be replaced by a serine (S). 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
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.041
.;T
Eigen
Benign
0.0045
Eigen_PC
Benign
-0.010
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-2.2
N;.
REVEL
Benign
0.13
Sift
Benign
0.033
D;.
Sift4G
Pathogenic
0.0
D;D
Vest4
0.19
MutPred
0.55
Gain of MoRF binding (P = 0.0497);Gain of MoRF binding (P = 0.0497);
MVP
0.48
ClinPred
0.75
D
GERP RS
4.5
Varity_R
0.086
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-201163305; API