Variant 1-160579424-T-A 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_003874.4(CD84):c.14A>T(p.His5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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

CD84
NM_003874.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.591

Variant links:

Genes affected

CD84 (HGNC:1704): (CD84 molecule) This gene encodes a membrane glycoprotein that is a member of the signaling lymphocyte activation molecule (SLAM) family. This family forms a subset of the larger CD2 cell-surface receptor Ig superfamily. The encoded protein is a homophilic adhesion molecule that is expressed in numerous immune cells types and is involved in regulating receptor-mediated signaling in those cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

CD84 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=0.08196822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD84	NM_003874.4 linkuse as main transcript	c.14A>T	p.His5Leu	missense_variant	1/7	ENST00000368054.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD84	ENST00000368054.8 linkuse as main transcript	c.14A>T	p.His5Leu	missense_variant	1/7	1	NM_003874.4		Q9UIB8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460982

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726776

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:

0.00000180

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

Dec 28, 2022

The c.14A>T (p.H5L) alteration is located in exon 1 (coding exon 1) of the CD84 gene. This alteration results from a A to T substitution at nucleotide position 14, causing the histidine (H) at amino acid position 5 to be replaced by a leucine (L). 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

0.093

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.1

DANN

Benign

0.88

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.27

T;T;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.082

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.98

N;N;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.054

T;T;T;T;T

Polyphen

0.0020

B;B;B;B;B

Vest4

0.11

MutPred

0.42

Gain of catalytic residue at H5 (P = 0.0038);Gain of catalytic residue at H5 (P = 0.0038);Gain of catalytic residue at H5 (P = 0.0038);Gain of catalytic residue at H5 (P = 0.0038);Gain of catalytic residue at H5 (P = 0.0038);

MVP

0.42

MPC

0.14

ClinPred

0.11

GERP RS

-1.7

Varity_R

0.075

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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