15-65384370-G-A

Variant names:

• chr15-65384370-G-A
• NM_020962.3:c.3392C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020962.3(IGDCC4):​c.3392C>T​(p.Ala1131Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGDCC4 NM_020962.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGDCC4	NM_020962.3	c.3392C>T	p.Ala1131Val	missense_variant	Exon 20 of 20	ENST00000352385.3	NP_066013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGDCC4	ENST00000352385.3	c.3392C>T	p.Ala1131Val	missense_variant	Exon 20 of 20	1	NM_020962.3	ENSP00000319623.3
IGDCC4	ENST00000559327.1	n.2661C>T		non_coding_transcript_exon_variant	Exon 14 of 14	1
IGDCC4	ENST00000558048.5	n.524C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3392C>T (p.A1131V) alteration is located in exon 20 (coding exon 20) of the IGDCC4 gene. This alteration results from a C to T substitution at nucleotide position 3392, causing the alanine (A) at amino acid position 1131 to be replaced by a valine (V). 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	0.34
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.0	L
PhyloP100		6.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.22		Gain of sheet (P = 0.0125);
MVP		0.67
MPC		1.0
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.34
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

hg19: chr15-65676708;