15-65329021-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004884.4(IGDCC3):​c.2333G>C​(p.Gly778Ala) 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. 15/21 in silico tools predict a benign 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. G778D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

IGDCC3
NM_004884.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.400
Variant links:
Genes affected
IGDCC3 (HGNC:9700): (immunoglobulin superfamily DCC subclass member 3) Predicted to act upstream of or within neuromuscular process controlling balance. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.09872529).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IGDCC3NM_004884.4 linkc.2333G>C p.Gly778Ala missense_variant Exon 14 of 14 ENST00000327987.9 NP_004875.2 Q8IVU1
IGDCC3XM_011522241.3 linkc.2330G>C p.Gly777Ala missense_variant Exon 14 of 14 XP_011520543.3
IGDCC3XM_011522243.1 linkc.1964G>C p.Gly655Ala missense_variant Exon 13 of 13 XP_011520545.1
IGDCC3XM_011522244.2 linkc.1922G>C p.Gly641Ala missense_variant Exon 13 of 13 XP_011520546.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGDCC3ENST00000327987.9 linkc.2333G>C p.Gly778Ala missense_variant Exon 14 of 14 1 NM_004884.4 ENSP00000332773.4 Q8IVU1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000825
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.067
T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.099
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.63
N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.61
N
REVEL
Benign
0.031
Sift
Uncertain
0.022
D
Sift4G
Benign
0.38
T
Polyphen
0.0010
B
Vest4
0.098
MutPred
0.19
Gain of helix (P = 0.0225);
MVP
0.50
MPC
0.072
ClinPred
0.12
T
GERP RS
2.2
Varity_R
0.066
gMVP
0.23

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs776810011; hg19: chr15-65621359; API