chr5-140632778-A-C

Position:

• chr5-140632778-A-C

Variant summary

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

The NM_000591.4(CD14):​c.206T>G​(p.Phe69Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.30

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD14	NM_000591.4	c.206T>G	p.Phe69Cys	missense_variant	2/2	ENST00000302014.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD14	ENST00000302014.11	c.206T>G	p.Phe69Cys	missense_variant	2/2	1	NM_000591.4	P1
CD14	ENST00000498971.7	c.206T>G	p.Phe69Cys	missense_variant	3/3	2		P1
CD14	ENST00000512545.2	c.206T>G	p.Phe69Cys	missense_variant	3/3	3		P1
CD14	ENST00000519715.2	c.206T>G	p.Phe69Cys	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

Jan 23, 2023

The c.206T>G (p.F69C) alteration is located in exon 3 (coding exon 2) of the CD14 gene. This alteration results from a T to G substitution at nucleotide position 206, causing the phenylalanine (F) at amino acid position 69 to be replaced by a cysteine (C). 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	0.85
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.46	T;T;.;T
Eigen	Benign	0.070
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.78	.;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	1.8	L;L;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;.;D
Polyphen		0.99	D;D;.;.
Vest4		0.57
MutPred		0.41		Gain of catalytic residue at P68 (P = 0.0088);Gain of catalytic residue at P68 (P = 0.0088);Gain of catalytic residue at P68 (P = 0.0088);Gain of catalytic residue at P68 (P = 0.0088);
MVP		0.99
MPC		1.5
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.33
gMVP		0.80

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-140012363;