NM_004884.4:c.2359G>A

Variant names:

• chr15-65328995-C-T
• rs777386122
• NM_004884.4:c.2359G>A

Variant summary

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

The NM_004884.4(IGDCC3):​c.2359G>A​(p.Asp787Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,610,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: IGDCC3 NM_004884.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 1 publications found

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

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=0.14666188).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004884.4. 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
	IGDCC3	NM_004884.4	MANE Select	c.2359G>A	p.Asp787Asn	missense	Exon 14 of 14	NP_004875.2	Q8IVU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGDCC3	ENST00000327987.9	TSL:1 MANE Select	c.2359G>A	p.Asp787Asn	missense	Exon 14 of 14	ENSP00000332773.4	Q8IVU1
	IGDCC3	ENST00000920202.1		c.2401G>A	p.Asp801Asn	missense	Exon 14 of 14	ENSP00000590261.1
	IGDCC3	ENST00000920210.1		c.2398G>A	p.Asp800Asn	missense	Exon 14 of 14	ENSP00000590269.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000828 AC: 2 AN: 241638 AF XY: 0.00000757

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458632 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725624

African (AFR) AF: 0.0000299 AC: 1 AN: 33398

American (AMR) AF: 0.0000452 AC: 2 AN: 44274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110904

Other (OTH) AF: 0.00 AC: 0 AN: 60216

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

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	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.084
Sift	Benign	0.098	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.42	B
Vest4		0.23
MutPred		0.13		Gain of glycosylation at P786 (P = 0.1399)
MVP		0.64
MPC		0.068
ClinPred		0.13	T
GERP RS		4.2
Varity_R		0.035
gMVP		0.17

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

dbSNP: rs777386122; hg19: chr15-65621333; COSMIC: COSV100031661; COSMIC: COSV100031661;