NM_016951.4:c.313A>G

Variant names:

• chr16-66563197-A-G
• NM_016951.4:c.313A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016951.4(CKLF):​c.313A>G​(p.Thr105Ala) 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. 13/21 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: CKLF NM_016951.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.200
• Publications: 0 publications found

Genes affected

CKLF (HGNC:13253): (chemokine like factor) The product of this gene is a cytokine. Cytokines are small proteins that have an essential role in the immune and inflammatory responses. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 16. The protein encoded by this gene is a potent chemoattractant for neutrophils, monocytes and lymphocytes. It also can stimulate the proliferation of skeletal muscle cells. This protein may play important roles in inflammation and in the regeneration of skeletal muscle. Alternatively spliced transcript variants encoding different isoforms have been identified. Naturally occurring read-through transcription occurs between this locus and the neighboring locus CMTM1 (CKLF-like MARVEL transmembrane domain containing 1).[provided by RefSeq, Feb 2011]

CKLF-CMTM1 (HGNC:39977): (CKLF-CMTM1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring CKLF (chemokine-like factor) and CMTM1 (CKLF-like MARVEL transmembrane domain containing 1) genes on chromosome 16. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047177672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016951.4. 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
	CKLF	NM_016951.4	MANE Select	c.313A>G	p.Thr105Ala	missense	Exon 3 of 4	NP_058647.1	Q9UBR5-1
	CKLF	NM_001040138.3		c.313A>G	p.Thr105Ala	missense	Exon 3 of 4	NP_001035228.1	Q9UBR5-5
	CKLF	NM_181640.2		c.154A>G	p.Thr52Ala	missense	Exon 2 of 3	NP_857591.1	Q5BJH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKLF	ENST00000264001.9	TSL:1 MANE Select	c.313A>G	p.Thr105Ala	missense	Exon 3 of 4	ENSP00000264001.5	Q9UBR5-1
	CKLF	ENST00000351137.8	TSL:1	c.154A>G	p.Thr52Ala	missense	Exon 2 of 3	ENSP00000264003.4	Q9UBR5-2
	CKLF-CMTM1	ENST00000616804.5	TSL:2	c.237+4849A>G		intron	N/A	ENSP00000479319.1	A0A087WVB3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.1
DANN	Benign	0.57
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.20
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.046
Sift	Benign	0.67	T
Sift4G	Benign	0.45	T
Polyphen		0.76	P
Vest4		0.13
MutPred		0.38		Loss of glycosylation at T105 (P = 0.0454)
MVP		0.13
MPC		0.14
ClinPred		0.11	T
GERP RS		-1.8
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.22

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

hg19: chr16-66597100; COSMIC: COSV50451522; COSMIC: COSV50451522;