NM_172217.5:c.772G>C

Variant names:

• chr15-81273186-G-C
• rs188062582
• NM_172217.5:c.772G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_172217.5(IL16):​c.772G>C​(p.Asp258His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D258Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL16 NM_172217.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.44
• Publications: 2 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85

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.772G>C	p.Asp258His	missense	Exon 6 of 19	NP_757366.2	Q14005-1
	IL16	NM_001352686.2		c.925G>C	p.Asp309His	missense	Exon 6 of 19	NP_001339615.1
	IL16	NM_001438661.1		c.913G>C	p.Asp305His	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.772G>C	p.Asp258His	missense	Exon 6 of 19	ENSP00000508085.1	Q14005-1
	IL16	ENST00000302987.10	TSL:1	c.913G>C	p.Asp305His	missense	Exon 6 of 19	ENSP00000302935.5	A0A8C8KBU6
	IL16	ENST00000909975.1		c.772G>C	p.Asp258His	missense	Exon 6 of 19	ENSP00000580034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		8.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.77		Loss of disorder (P = 0.1379)
MVP		0.46
MPC		0.58
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.71
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs188062582; hg19: chr15-81565527;