rs776810011

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-65329021-C-A
• chr15-65329021-C-G
• chr15-65329021-C-T

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>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. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• 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=0.16004941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGDCC3	NM_004884.4	c.2333G>T	p.Gly778Val	missense_variant	Exon 14 of 14	ENST00000327987.9	NP_004875.2
IGDCC3	XM_011522241.3	c.2330G>T	p.Gly777Val	missense_variant	Exon 14 of 14		XP_011520543.3
IGDCC3	XM_011522243.1	c.1964G>T	p.Gly655Val	missense_variant	Exon 13 of 13		XP_011520545.1
IGDCC3	XM_011522244.2	c.1922G>T	p.Gly641Val	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>T	p.Gly778Val	missense_variant	Exon 14 of 14	1	NM_004884.4	ENSP00000332773.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-65621359;