Variant 15-65386567-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020962.3(IGDCC4):c.2935C>T(p.Arg979Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 1,453,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

IGDCC4
NM_020962.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGDCC4	NM_020962.3 linkuse as main transcript	c.2935C>T	p.Arg979Cys	missense_variant	17/20	ENST00000352385.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGDCC4	ENST00000352385.3 linkuse as main transcript	c.2935C>T	p.Arg979Cys	missense_variant	17/20	1	NM_020962.3	P1	Q8TDY8-1
IGDCC4	ENST00000559327.1 linkuse as main transcript	n.2204C>T		non_coding_transcript_exon_variant	11/14	1
IGDCC4	ENST00000560319.1 linkuse as main transcript	n.79C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000300

AC:

AN:

233112

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

126238

show subpopulations

Gnomad AFR exome

AF:

0.0000678

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000561

Gnomad NFE exome

AF:

0.00000944

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000234

AC:

AN:

1453366

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

722244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000824

AC:

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

May 17, 2023

The c.2935C>T (p.R979C) alteration is located in exon 17 (coding exon 17) of the IGDCC4 gene. This alteration results from a C to T substitution at nucleotide position 2935, causing the arginine (R) at amino acid position 979 to be replaced by a cysteine (C). 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

0.32

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.018

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.7

REVEL

Benign

0.26

Sift

Benign

0.11

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.78

MutPred

0.51

Loss of sheet (P = 0.0315);

MVP

0.58

MPC

1.2

ClinPred

0.32

GERP RS

5.3

Varity_R

0.10

gMVP

0.65

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