dbSNP rs119477056: CD96:p.Thr264Lys (chr3-111585362-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_005816.5(CD96):c.791C>A(p.Thr264Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T264M) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CD96
NM_005816.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

CD96 (HGNC:16892): (CD96 molecule) The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein. The protein may play a role in the adhesive interactions of activated T and NK cells during the late phase of the immune response. It may also function in antigen presentation. Alternative splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

CD96 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;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr3-111585362-C-T is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.15481901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD96	NM_005816.5 link	c.791C>A	p.Thr264Lys	missense_variant	Exon 5 of 14	ENST00000352690.9	NP_005807.1	P40200-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD96	ENST00000352690.9 link	c.791C>A	p.Thr264Lys	missense_variant	Exon 5 of 14	1	NM_005816.5	ENSP00000342040.3	P40200-2
CD96	ENST00000283285.10 link	c.839C>A	p.Thr280Lys	missense_variant	Exon 6 of 15	1		ENSP00000283285.5	P40200-1
CD96	ENST00000438817.6 link	c.791C>A	p.Thr264Lys	missense_variant	Exon 5 of 8	1		ENSP00000389801.2	Q8WUE2
CD96	ENST00000494798.1 link	n.791C>A		non_coding_transcript_exon_variant	Exon 5 of 15	2		ENSP00000417152.1	E9PEJ1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724638

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.24

DANN

Benign

0.73

DEOGEN2

Benign

0.039

.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

.;L;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.12

T;D;T

Sift4G

Benign

0.088

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.50

MutPred

0.66

.;Gain of ubiquitination at T280 (P = 0.0138);.;

MVP

0.55

MPC

0.067

ClinPred

0.099

GERP RS

-5.3

Varity_R

0.072

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over