chr15-65329021-C-A

Variant names:

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

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.2333G>T​(p.Gly778Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. G778S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IGDCC3 NM_004884.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 0 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=0.16004941).

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.2333G>T	p.Gly778Val	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.2333G>T	p.Gly778Val	missense	Exon 14 of 14	ENSP00000332773.4	Q8IVU1
	IGDCC3	ENST00000920202.1		c.2375G>T	p.Gly792Val	missense	Exon 14 of 14	ENSP00000590261.1
	IGDCC3	ENST00000920210.1		c.2372G>T	p.Gly791Val	missense	Exon 14 of 14	ENSP00000590269.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459968 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726304

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111382

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.40
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.068
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.046	D
Polyphen		0.45	B
Vest4		0.23
MutPred		0.26		Loss of loop (P = 0.0235)
MVP		0.54
MPC		0.082
ClinPred		0.60	D
GERP RS		2.2
Varity_R		0.074
gMVP		0.32
Mutation Taster		=90/10	polymorphism

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: rs776810011; hg19: chr15-65621359;