Variant chr12-9755093-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_001781.2(CD69):c.356C>T(p.Thr119Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,768 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: 0.0000041 ( 0 hom. )

Consequence

CD69
NM_001781.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

Variant links:

Genes affected

CD69 (HGNC:1694): (CD69 molecule) This gene encodes a member of the calcium dependent lectin superfamily of type II transmembrane receptors. Expression of the encoded protein is induced upon activation of T lymphocytes, and may play a role in proliferation. Furthermore, the protein may act to transmit signals in natural killer cells and platelets. [provided by RefSeq, Aug 2011]

CD69 links:

CD69 (HGNC:):

CD69 links:

Genome browser will be placed here

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	Protein	UniProt
CD69	NM_001781.2 linkuse as main transcript	c.356C>T	p.Thr119Ile	missense_variant	3/5	ENST00000228434.7	NP_001772.1	Q07108Q53ZX0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD69	ENST00000228434.7 linkuse as main transcript	c.356C>T	p.Thr119Ile	missense_variant	3/5	1	NM_001781.2	ENSP00000228434.3	Q07108
CD69	ENST00000536709.1 linkuse as main transcript	c.356C>T	p.Thr119Ile	missense_variant	3/4	2		ENSP00000442597.1	B4E009
CD69	ENST00000416624.6 linkuse as main transcript	n.437C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251350

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727184

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 22, 2021

The c.356C>T (p.T119I) alteration is located in exon 3 (coding exon 3) of the CD69 gene. This alteration results from a C to T substitution at nucleotide position 356, causing the threonine (T) at amino acid position 119 to be replaced by an isoleucine (I). 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

0.31

BayesDel_addAF

Benign

0.00088

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0068

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.055

T;T

Polyphen

1.0

D;.

Vest4

0.44

MutPred

0.70

Loss of disorder (P = 0.0736);Loss of disorder (P = 0.0736);

MVP

0.61

MPC

0.27

ClinPred

0.97

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.44

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