NM_004363.6:c.106C>T

Variant names:

• chr19-41709721-C-T
• NM_004363.6:c.106C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004363.6(CEACAM5):​c.106C>T​(p.Leu36Phe) 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. 13/19 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: CEACAM5 NM_004363.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.01

Genes affected

CEACAM5 (HGNC:1817): (CEA cell adhesion molecule 5) This gene encodes a cell surface glycoprotein that represents the founding member of the carcinoembryonic antigen (CEA) family of proteins. The encoded protein is used as a clinical biomarker for gastrointestinal cancers and may promote tumor development through its role as a cell adhesion molecule. Additionally, the encoded protein may regulate differentiation, apoptosis, and cell polarity. This gene is present in a CEA family gene cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ENSG00000267881 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1335114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM5	NM_004363.6	c.106C>T	p.Leu36Phe	missense_variant	Exon 2 of 10	ENST00000221992.11	NP_004354.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM5	ENST00000221992.11	c.106C>T	p.Leu36Phe	missense_variant	Exon 2 of 10	1	NM_004363.6	ENSP00000221992.5
ENSG00000267881	ENST00000435837.2	c.64+926C>T		intron_variant	Intron 1 of 1	3		ENSP00000469926.1

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

Jan 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106C>T (p.L36F) alteration is located in exon 2 (coding exon 2) of the CEACAM5 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the leucine (L) at amino acid position 36 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	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.076	.;T;T;T;T;T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.76	.;.;T;T;T;.;.
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	.;N;.;.;.;N;.
REVEL	Benign	0.056
Sift	Uncertain	0.019	.;D;.;.;.;D;.
Sift4G	Benign	0.070	T;T;T;D;T;T;T
Vest4		0.042
MutPred		0.39		Gain of methylation at K35 (P = 0.0314);Gain of methylation at K35 (P = 0.0314);Gain of methylation at K35 (P = 0.0314);Gain of methylation at K35 (P = 0.0314);Gain of methylation at K35 (P = 0.0314);Gain of methylation at K35 (P = 0.0314);Gain of methylation at K35 (P = 0.0314);
MVP		0.17
MPC		0.45
ClinPred		0.36	T
GERP RS		-6.2
gMVP		0.19

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: chr19-42213640;