19-41797727-A-G

Variant names:

• chr19-41797727-A-G
• NM_001815.5:c.203A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001815.5(CEACAM3):​c.203A>G​(p.Tyr68Cys) 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: CEACAM3 NM_001815.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.02

Genes affected

CEACAM3 (HGNC:1815): (CEA cell adhesion molecule 3) This gene encodes a member of the family of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), which are used by several bacterial pathogens to bind and invade host cells. The encoded transmembrane protein directs phagocytosis of several bacterial species that is dependent on the small GTPase Rac. It is thought to serve an important role in controlling human-specific pathogens by the innate immune system. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM3	NM_001815.5	c.203A>G	p.Tyr68Cys	missense_variant	Exon 2 of 7	ENST00000357396.8	NP_001806.2
CEACAM3	NM_001277163.3	c.203A>G	p.Tyr68Cys	missense_variant	Exon 2 of 6		NP_001264092.1
CEACAM3	NR_102333.3	n.294A>G		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM3	ENST00000357396.8	c.203A>G	p.Tyr68Cys	missense_variant	Exon 2 of 7	1	NM_001815.5	ENSP00000349971.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.203A>G (p.Y68C) alteration is located in exon 2 (coding exon 2) of the CEACAM3 gene. This alteration results from a A to G substitution at nucleotide position 203, causing the tyrosine (Y) at amino acid position 68 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	0.61
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;.;.;T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.82	T;T;.;T
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.92	D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.8	H;H;H;.
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-8.0	D;.;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;.;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.41
MutPred		0.86		Gain of methylation at K69 (P = 0.0203);Gain of methylation at K69 (P = 0.0203);Gain of methylation at K69 (P = 0.0203);.;
MVP		0.69
MPC		0.55
ClinPred		0.96	D
GERP RS		2.4
Varity_R		0.66
gMVP		0.52

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: chr19-42301659;