rs119477056

chr3-111585362-C-Achr3-111585362-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_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 Pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD96 NM_005816.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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]

ACMG classification

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 ClinVar as [Pathogenic]. Clinvar id is 4640.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.15481901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD96	NM_005816.5	c.791C>A	p.Thr264Lys	missense_variant	5/14	ENST00000352690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD96	ENST00000352690.9	c.791C>A	p.Thr264Lys	missense_variant	5/14	1	NM_005816.5	P2
CD96	ENST00000283285.10	c.839C>A	p.Thr280Lys	missense_variant	6/15	1		A2
CD96	ENST00000438817.6	c.791C>A	p.Thr264Lys	missense_variant	5/8	1		A2
CD96	ENST00000494798.1	c.791C>A	p.Thr264Lys	missense_variant, NMD_transcript_variant	5/15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455724 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 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.: 32

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	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.24
Dann	Benign	0.73
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
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	T
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

Other links and lift over

dbSNP: rs119477056; hg19: chr3-111304209; COSMIC: COSV51920348;