Variant chr19-10290081-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003259.4(ICAM5):c.38T>G(p.Leu13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,391,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ICAM5
NM_003259.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

ICAM5 (HGNC:5348): (intercellular adhesion molecule 5) The protein encoded by this gene is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins, contain 2-9 immunoglobulin-like C2-type domains, and bind to the leukocyte adhesion LFA-1 protein. This protein is expressed on the surface of telencephalic neurons and displays two types of adhesion activity, homophilic binding between neurons and heterophilic binding between neurons and leukocytes. It may be a critical component in neuron-microglial cell interactions in the course of normal development or as part of neurodegenerative diseases. [provided by RefSeq, Jul 2008]

ICAM5 links:

ICAM5 (HGNC:):

ICAM5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICAM5	NM_003259.4 linkuse as main transcript	c.38T>G	p.Leu13Arg	missense_variant	1/11	ENST00000221980.5	NP_003250.3	Q9UMF0Q8N6I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ICAM5	ENST00000221980.5 linkuse as main transcript	c.38T>G	p.Leu13Arg	missense_variant	1/11	1	NM_003259.4	ENSP00000221980.3	Q9UMF0
ICAM5	ENST00000586004.1 linkuse as main transcript	n.58T>G		non_coding_transcript_exon_variant	1/3	4
ICAM5	ENST00000588912.1 linkuse as main transcript	n.89T>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1391258

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

686046

show subpopulations

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:

0.00000186

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

Mar 18, 2024

The c.38T>G (p.L13R) alteration is located in exon 1 (coding exon 1) of the ICAM5 gene. This alteration results from a T to G substitution at nucleotide position 38, causing the leucine (L) at amino acid position 13 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

Eigen

Benign

0.17

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.53

M_CAP

Benign

0.082

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

REVEL

Benign

0.28

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.036

Polyphen

0.98

Vest4

0.79

MutPred

0.68

Gain of MoRF binding (P = 0.0011);

MVP

0.73

ClinPred

0.92

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.42

gMVP

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over