Genetic Variant IGDCC3:p.Asp787Asn (chr15-65328995-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 14/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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]

IGDCC3 links:

Genome browser will be placed here

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=0.14666188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGDCC3	NM_004884.4 link	c.2359G>A	p.Asp787Asn	missense_variant	Exon 14 of 14	ENST00000327987.9	NP_004875.2	Q8IVU1
IGDCC3	XM_011522241.3 link	c.2356G>A	p.Asp786Asn	missense_variant	Exon 14 of 14		XP_011520543.3
IGDCC3	XM_011522243.1 link	c.1990G>A	p.Asp664Asn	missense_variant	Exon 13 of 13		XP_011520545.1
IGDCC3	XM_011522244.2 link	c.1948G>A	p.Asp650Asn	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 link	c.2359G>A	p.Asp787Asn	missense_variant	Exon 14 of 14	1	NM_004884.4	ENSP00000332773.4		Q8IVU1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00000828

AC:

AN:

241638

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132162

show subpopulations

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 SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458632

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2359G>A (p.D787N) alteration is located in exon 14 (coding exon 14) of the IGDCC3 gene. This alteration results from a G to A substitution at nucleotide position 2359, causing the aspartic acid (D) at amino acid position 787 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.53

M_CAP

Benign

0.027

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.29

REVEL

Benign

0.084

Sift

Benign

0.098

Sift4G

Pathogenic

0.0

Polyphen

0.42

Vest4

0.23

MutPred

0.13

Gain of glycosylation at P786 (P = 0.1399);

MVP

0.64

MPC

0.068

ClinPred

0.13

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over