1-160950696-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080878.3(ITLN2):​c.457G>A​(p.Asp153Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D153Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ITLN2
NM_080878.3 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.97
Variant links:
Genes affected
ITLN2 (HGNC:20599): (intelectin 2) Predicted to enable oligosaccharide binding activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITLN2NM_080878.3 linkc.457G>A p.Asp153Asn missense_variant Exon 5 of 8 ENST00000368029.4 NP_543154.1 Q8WWU7-1
ITLN2XM_024453321.2 linkc.454G>A p.Asp152Asn missense_variant Exon 5 of 8 XP_024309089.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITLN2ENST00000368029.4 linkc.457G>A p.Asp153Asn missense_variant Exon 5 of 8 1 NM_080878.3 ENSP00000357008.3 Q8WWU7-1
ITLN2ENST00000490489.1 linkn.448G>A non_coding_transcript_exon_variant Exon 2 of 2 3
ITLN2ENST00000494442.1 linkn.317G>A non_coding_transcript_exon_variant Exon 1 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249484
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134856
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1460908
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726734
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000330
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.081
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.018
T
MetaRNN
Pathogenic
0.85
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.17
Sift
Benign
0.10
T
Sift4G
Uncertain
0.053
T
Polyphen
1.0
D
Vest4
0.41
MutPred
0.85
Gain of ubiquitination at K157 (P = 0.0671);
MVP
0.40
MPC
0.59
ClinPred
0.89
D
GERP RS
3.5
Varity_R
0.065
gMVP
0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747282302; hg19: chr1-160920486; API