3-111567526-C-G

Position:

• chr3-111567526-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005816.5(CD96):​c.422C>G​(p.Thr141Arg) 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. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD96 NM_005816.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.296

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 (HGNC:):

ACMG classification

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
CD96	NM_005816.5	c.422C>G	p.Thr141Arg	missense_variant	3/14	ENST00000352690.9	NP_005807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD96	ENST00000352690.9	c.422C>G	p.Thr141Arg	missense_variant	3/14	1	NM_005816.5	ENSP00000342040.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 25, 2021

Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.5
DANN	Benign	0.95
DEOGEN2	Benign	0.052	.;T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.95	P;P;P
Vest4		0.28
MutPred		0.39		Loss of catalytic residue at H139 (P = 0.0946);Loss of catalytic residue at H139 (P = 0.0946);Loss of catalytic residue at H139 (P = 0.0946);
MVP		0.60
MPC		0.020
ClinPred		0.15	T
GERP RS		0.53
Varity_R		0.089
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.43		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-111286373;