NM_004363.6:c.104A>G

Variant names:

• chr19-41709719-A-G
• NM_004363.6:c.104A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004363.6(CEACAM5):​c.104A>G​(p.Lys35Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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: 3.80
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08728507).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004363.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM5	NM_004363.6	MANE Select	c.104A>G	p.Lys35Arg	missense	Exon 2 of 10	NP_004354.3	A0A024R0K5
	CEACAM5	NM_001291484.3		c.104A>G	p.Lys35Arg	missense	Exon 2 of 10	NP_001278413.1	P06731-1
	CEACAM5	NM_001308398.3		c.104A>G	p.Lys35Arg	missense	Exon 2 of 10	NP_001295327.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM5	ENST00000221992.11	TSL:1 MANE Select	c.104A>G	p.Lys35Arg	missense	Exon 2 of 10	ENSP00000221992.5	P06731-1
	CEACAM5	ENST00000405816.5	TSL:1	c.104A>G	p.Lys35Arg	missense	Exon 2 of 10	ENSP00000385072.1	P06731-1
	CEACAM5	ENST00000617332.4	TSL:1	c.104A>G	p.Lys35Arg	missense	Exon 2 of 9	ENSP00000482303.1	P06731-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.8
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.053
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.056	T
Vest4		0.091
MutPred		0.40		Loss of ubiquitination at K35 (P = 0.0141)
MVP		0.52
MPC		0.18
ClinPred		0.26	T
GERP RS		3.1
PromoterAI		0.00010	Neutral
gMVP		0.14
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr19-42213638;