chr1-201194177-C-T

Variant names:

• chr1-201194177-C-T
• rs189690117
• NM_001164586.2:c.31C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11
• 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.

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

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.31C>T	p.Pro11Ser	missense	Exon 3 of 24	NP_001158058.1	Q86VF2-5
	IGFN1	NM_001367841.1		c.31C>T	p.Pro11Ser	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.31C>T	p.Pro11Ser	missense	Exon 3 of 24	ENSP00000334714.4	Q86VF2-5
	IGFN1	ENST00000437879.6	TSL:1	n.31C>T		non_coding_transcript_exon	Exon 3 of 26	ENSP00000399041.2	Q86VF2-4
	IGFN1	ENST00000295591.12	TSL:5	c.31C>T	p.Pro11Ser	missense	Exon 3 of 25	ENSP00000295591.9	Q86VF2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.34
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
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.13
Sift	Benign	0.033	D
Sift4G	Pathogenic	0.0	D
Vest4		0.19
MutPred		0.55		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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs189690117; hg19: chr1-201163305;