15-81273108-G-T

Variant names:

• chr15-81273108-G-T
• rs776826431
• NM_172217.5:c.694G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_172217.5(IL16):​c.694G>T​(p.Val232Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V232A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IL16 NM_172217.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.44
• Publications: 0 publications found

Genes affected

IL16 (HGNC:5980): (interleukin 16) The protein encoded by this gene is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of this cytokine is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. The cytokine function is exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172217.5. 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
	IL16	NM_172217.5	MANE Select	c.694G>T	p.Val232Phe	missense	Exon 6 of 19	NP_757366.2	Q14005-1
	IL16	NM_001352686.2		c.847G>T	p.Val283Phe	missense	Exon 6 of 19	NP_001339615.1
	IL16	NM_001438661.1		c.835G>T	p.Val279Phe	missense	Exon 6 of 19	NP_001425590.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	ENST00000683961.1	MANE Select	c.694G>T	p.Val232Phe	missense	Exon 6 of 19	ENSP00000508085.1	Q14005-1
	IL16	ENST00000302987.10	TSL:1	c.835G>T	p.Val279Phe	missense	Exon 6 of 19	ENSP00000302935.5	A0A8C8KBU6
	IL16	ENST00000909975.1		c.694G>T	p.Val232Phe	missense	Exon 6 of 19	ENSP00000580034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461008 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726842

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111436

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.050	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		8.4
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.74		Gain of ubiquitination at K235 (P = 0.1375)
MVP		0.63
MPC		0.62
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.66
gMVP		0.76
Mutation Taster		=28/72	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs776826431; hg19: chr15-81565449;