NM_001007237.3:c.3214C>T

Variant names:

• chr1-116579512-G-A
• NM_001007237.3:c.3214C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007237.3(IGSF3):​c.3214C>T​(p.Pro1072Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGSF3 NM_001007237.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

IGSF3 (HGNC:5950): (immunoglobulin superfamily member 3) The protein encoded by this gene is an immunoglobulin-like membrane protein containing several V-type Ig-like domains. A mutation in this gene has been associated with bilateral nasolacrimal duct obstruction (LCDD). [provided by RefSeq, Jun 2016]

IGSF3 Gene-Disease associations (from GenCC):

• familial congenital nasolacrimal duct obstruction

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

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=0.09681395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007237.3. 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
	IGSF3	NM_001007237.3	MANE Select	c.3214C>T	p.Pro1072Ser	missense	Exon 10 of 11	NP_001007238.1	O75054-1
	IGSF3	NM_001542.4		c.3274C>T	p.Pro1092Ser	missense	Exon 11 of 12	NP_001533.2	O75054-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF3	ENST00000369486.8	TSL:1 MANE Select	c.3214C>T	p.Pro1072Ser	missense	Exon 10 of 11	ENSP00000358498.4	O75054-1
	IGSF3	ENST00000318837.6	TSL:2	c.3274C>T	p.Pro1092Ser	missense	Exon 10 of 11	ENSP00000321184.6	O75054-2
	IGSF3	ENST00000369483.5	TSL:5	c.3274C>T	p.Pro1092Ser	missense	Exon 11 of 12	ENSP00000358495.1	O75054-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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	Benign	0.10
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	N
PhyloP100		2.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.16	T
Sift4G	Benign	0.54	T
Polyphen		0.011	B
Vest4		0.20
MutPred		0.41		Gain of disorder (P = 0.0957)
MVP		0.78
MPC		0.62
ClinPred		0.30	T
GERP RS		4.7
Varity_R		0.052
gMVP		0.46
Mutation Taster		=93/7	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

hg19: chr1-117122134;