3-111545115-C-A

Variant names:

• chr3-111545115-C-A
• rs557620368
• NM_005816.5:c.131C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005816.5(CD96):​c.131C>A​(p.Thr44Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T44I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD96 NM_005816.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• C syndrome

  Inheritance: AD, Unknown, AR Classification: LIMITED Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005816.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD96	NM_005816.5	MANE Select	c.131C>A	p.Thr44Asn	missense	Exon 2 of 14	NP_005807.1	P40200-2
	CD96	NM_198196.3		c.131C>A	p.Thr44Asn	missense	Exon 2 of 15	NP_937839.1	P40200-1
	CD96	NM_001410800.1		c.131C>A	p.Thr44Asn	missense	Exon 2 of 14	NP_001397729.1	E9PEJ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD96	ENST00000352690.9	TSL:1 MANE Select	c.131C>A	p.Thr44Asn	missense	Exon 2 of 14	ENSP00000342040.3	P40200-2
	CD96	ENST00000283285.10	TSL:1	c.131C>A	p.Thr44Asn	missense	Exon 2 of 15	ENSP00000283285.5	P40200-1
	CD96	ENST00000438817.6	TSL:1	c.131C>A	p.Thr44Asn	missense	Exon 2 of 8	ENSP00000389801.2	Q8WUE2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.054
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.087
Sift	Benign	0.088	T
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.46		Loss of sheet (P = 0.0817)
MVP		0.25
MPC		0.16
ClinPred		0.83	D
GERP RS		4.3
Varity_R		0.30
gMVP		0.61
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs557620368; hg19: chr3-111263962;