1-116577443-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001007237.3(IGSF3):c.3454C>T(p.Arg1152Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
IGSF3
NM_001007237.3 missense
NM_001007237.3 missense
Scores
4
8
5
Clinical Significance
Conservation
PhyloP100: 3.57
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, IGSF3
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGSF3 | NM_001007237.3 | c.3454C>T | p.Arg1152Trp | missense_variant | 11/11 | ENST00000369486.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGSF3 | ENST00000369486.8 | c.3454C>T | p.Arg1152Trp | missense_variant | 11/11 | 1 | NM_001007237.3 | P4 | |
IGSF3 | ENST00000318837.6 | c.3514C>T | p.Arg1172Trp | missense_variant | 11/11 | 2 | A1 | ||
IGSF3 | ENST00000369483.5 | c.3514C>T | p.Arg1172Trp | missense_variant | 12/12 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251496Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135922
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727246
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74436
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2023 | The c.3514C>T (p.R1172W) alteration is located in exon 12 (coding exon 11) of the IGSF3 gene. This alteration results from a C to T substitution at nucleotide position 3514, causing the arginine (R) at amino acid position 1172 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;.
Vest4
MutPred
0.44
.;Loss of disorder (P = 0.0089);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at