15-65329021-C-G

Variant names:

• chr15-65329021-C-G
• rs776810011
• NM_004884.4:c.2333G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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]

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=0.09872529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGDCC3	NM_004884.4	c.2333G>C	p.Gly778Ala	missense_variant	Exon 14 of 14	ENST00000327987.9	NP_004875.2
IGDCC3	XM_011522241.3	c.2330G>C	p.Gly777Ala	missense_variant	Exon 14 of 14		XP_011520543.3
IGDCC3	XM_011522243.1	c.1964G>C	p.Gly655Ala	missense_variant	Exon 13 of 13		XP_011520545.1
IGDCC3	XM_011522244.2	c.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
IGDCC3	ENST00000327987.9	c.2333G>C	p.Gly778Ala	missense_variant	Exon 14 of 14	1	NM_004884.4	ENSP00000332773.4

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

Other links and lift over

dbSNP: rs776810011; hg19: chr15-65621359;