chr5-140632470-G-A

Position:

• chr5-140632470-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000591.4(CD14):​c.514C>T​(p.Leu172Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD14 NM_000591.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

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:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD14	NM_000591.4	c.514C>T	p.Leu172Phe	missense_variant	2/2	ENST00000302014.11	NP_000582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD14	ENST00000302014.11	c.514C>T	p.Leu172Phe	missense_variant	2/2	1	NM_000591.4	ENSP00000304236.6
CD14	ENST00000498971.7	c.514C>T	p.Leu172Phe	missense_variant	3/3	2		ENSP00000426543.2
CD14	ENST00000512545.2	c.514C>T	p.Leu172Phe	missense_variant	3/3	3		ENSP00000425447.2
CD14	ENST00000519715.2	c.514C>T	p.Leu172Phe	missense_variant	3/3	4		ENSP00000430884.2

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

Aug 26, 2024

The c.514C>T (p.L172F) alteration is located in exon 3 (coding exon 2) of the CD14 gene. This alteration results from a C to T substitution at nucleotide position 514, causing the leucine (L) at amino acid position 172 to be replaced by a phenylalanine (F). 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	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;T;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N;N;D
REVEL	Uncertain	0.30
Sift	Benign	0.070	T;T;D
Sift4G	Uncertain	0.017	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.56
MutPred		0.56		Gain of methylation at K173 (P = 0.0346);Gain of methylation at K173 (P = 0.0346);Gain of methylation at K173 (P = 0.0346);
MVP		0.84
MPC		1.5
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.36
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-140012055; COSMIC: COSV57371260; COSMIC: COSV57371260;