1-201197261-C-T

Variant names:

• chr1-201197261-C-T
• rs1666959186
• NM_001164586.2:c.311C>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.311C>T​(p.Thr104Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: IGFN1 NM_001164586.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.720
• 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=0.15538046).

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.311C>T	p.Thr104Ile	missense	Exon 5 of 24	NP_001158058.1	Q86VF2-5
	IGFN1	NM_001367841.1		c.311C>T	p.Thr104Ile	missense	Exon 5 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.311C>T	p.Thr104Ile	missense	Exon 5 of 24	ENSP00000334714.4	Q86VF2-5
	IGFN1	ENST00000437879.6	TSL:1	n.311C>T		non_coding_transcript_exon	Exon 5 of 26	ENSP00000399041.2	Q86VF2-4
	IGFN1	ENST00000295591.12	TSL:5	c.311C>T	p.Thr104Ile	missense	Exon 5 of 25	ENSP00000295591.9	Q86VF2-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.3
DANN	Benign	0.57
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.72
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.023
Sift	Benign	0.067	T
Sift4G	Uncertain	0.029	D
Vest4		0.23
MutPred		0.47		Loss of phosphorylation at T104 (P = 0.0801)
MVP		0.34
ClinPred		0.12	T
GERP RS		-0.033
Varity_R		0.070
gMVP		0.50
Mutation Taster		=91/9	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: rs1666959186; hg19: chr1-201166389;