5-140632424-C-G

Position:

• chr5-140632424-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000591.4(CD14):​c.560G>C​(p.Cys187Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD14 NM_000591.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73

Genes affected

CD14 (HGNC:1628): (CD14 molecule) The protein encoded by this gene is a surface antigen that is preferentially expressed on monocytes/macrophages. It cooperates with other proteins to mediate the innate immune response to bacterial lipopolysaccharide, and to viruses. This gene has been identified as a target candidate in the treatment of SARS-CoV-2-infected patients to potentially lessen or inhibit a severe inflammatory response. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2020]

TMCO6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD14	NM_000591.4	c.560G>C	p.Cys187Ser	missense_variant	2/2	ENST00000302014.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD14	ENST00000302014.11	c.560G>C	p.Cys187Ser	missense_variant	2/2	1	NM_000591.4	P1
CD14	ENST00000498971.7	c.560G>C	p.Cys187Ser	missense_variant	3/3	2		P1
CD14	ENST00000512545.2	c.560G>C	p.Cys187Ser	missense_variant	3/3	3		P1
CD14	ENST00000519715.2	c.560G>C	p.Cys187Ser	missense_variant	3/3	4		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

The c.560G>C (p.C187S) alteration is located in exon 3 (coding exon 2) of the CD14 gene. This alteration results from a G to C substitution at nucleotide position 560, causing the cysteine (C) at amino acid position 187 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	28
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.48	T;T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.69	.;T;T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	0.092	D
MutationAssessor	Uncertain	2.0	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.3	D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.028	D;D;D
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		0.24	B;B;.
Vest4		0.75
MutPred		0.65		Gain of disorder (P = 6e-04);Gain of disorder (P = 6e-04);Gain of disorder (P = 6e-04);
MVP		0.87
MPC		0.75
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.79
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-140012009;