chr1-201194177-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11

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

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
IGFN1	NM_001164586.2	c.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
IGFN1	ENST00000335211.9	c.31C>T	p.Pro11Ser	missense_variant	Exon 3 of 24	5	NM_001164586.2	ENSP00000334714.4
IGFN1	ENST00000437879.6	n.31C>T		non_coding_transcript_exon_variant	Exon 3 of 26	1		ENSP00000399041.2
IGFN1	ENST00000295591.12	c.31C>T	p.Pro11Ser	missense_variant	Exon 3 of 25	5		ENSP00000295591.9

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

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;