Variant chr15-65385010-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020962.3(IGDCC4):c.3286C>G(p.Pro1096Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,457,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1096T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

IGDCC4
NM_020962.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

Variant links:

Genes affected

IGDCC4 (HGNC:13770): (immunoglobulin superfamily DCC subclass member 4) Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

IGDCC4 links:

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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=0.17285243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGDCC4	NM_020962.3 linkuse as main transcript	c.3286C>G	p.Pro1096Ala	missense_variant	19/20	ENST00000352385.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGDCC4	ENST00000352385.3 linkuse as main transcript	c.3286C>G	p.Pro1096Ala	missense_variant	19/20	1	NM_020962.3	P1	Q8TDY8-1
IGDCC4	ENST00000559327.1 linkuse as main transcript	n.2555C>G		non_coding_transcript_exon_variant	13/14	1
IGDCC4	ENST00000558048.5 linkuse as main transcript	n.418C>G		non_coding_transcript_exon_variant	2/3	2
IGDCC4	ENST00000561309.1 linkuse as main transcript	n.307C>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000291

AC:

AN:

240806

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131638

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000210

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000823

AC:

AN:

1457484

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000205

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

The c.3286C>G (p.P1096A) alteration is located in exon 19 (coding exon 19) of the IGDCC4 gene. This alteration results from a C to G substitution at nucleotide position 3286, causing the proline (P) at amino acid position 1096 to be replaced by an alanine (A). 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

0.077

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

M_CAP

Benign

0.041

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.2

REVEL

Benign

0.063

Sift

Benign

0.079

Sift4G

Benign

0.10

Polyphen

0.13

Vest4

0.40

MutPred

0.44

Loss of glycosylation at P1096 (P = 0.0123);

MVP

0.52

MPC

0.29

ClinPred

0.10

GERP RS

5.2

Varity_R

0.14

gMVP

0.24

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