rs752949676

Variant names:

• chr3-111579338-G-A
• rs752949676
• ENST00000465428.1:c.378G>A
• CD96 p.Trp126*

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The ENST00000465428.1(CD96):​c.378G>A​(p.Trp126*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 626,654 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (1 hom.)
• Consequence: CD96 ENST00000465428.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• 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: Unknown, AD, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

ACMG classification

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

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465428.1. 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.751+104G>A		intron	N/A	NP_005807.1	P40200-2
	CD96	NM_198196.3		c.799+104G>A		intron	N/A	NP_937839.1	P40200-1
	CD96	NM_001410800.1		c.751+104G>A		intron	N/A	NP_001397729.1	E9PEJ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD96	ENST00000465428.1	TSL:1	c.378G>A	p.Trp126*	stop_gained	Exon 2 of 2	ENSP00000417150.1	H7C4F0
	CD96	ENST00000352690.9	TSL:1 MANE Select	c.751+104G>A		intron	N/A	ENSP00000342040.3	P40200-2
	CD96	ENST00000283285.10	TSL:1	c.799+104G>A		intron	N/A	ENSP00000283285.5	P40200-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000180 AC: 4 AN: 221648 AF XY: 0.0000249

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000112 AC: 7 AN: 626654 Hom.: 1 Cov.: 6 AF XY: 0.0000147 AC XY: 5 AN XY: 340498

African (AFR) AF: 0.00 AC: 0 AN: 17576

American (AMR) AF: 0.00 AC: 0 AN: 41338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20826

East Asian (EAS) AF: 0.00 AC: 0 AN: 35522

South Asian (SAS) AF: 0.0000588 AC: 4 AN: 68038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51232

Middle Eastern (MID) AF: 0.000482 AC: 2 AN: 4150

European-Non Finnish (NFE) AF: 0.00000282 AC: 1 AN: 354960

Other (OTH) AF: 0.00 AC: 0 AN: 33012

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Uncertain	24
DANN	Benign	0.64
PhyloP100		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.86		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.86		Position offset: -4

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs752949676;

hg19: chr3-111298185;