chr19-41797793-C-T

Variant names:

• chr19-41797793-C-T
• NM_001815.5:c.269C>T

Variant summary

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

The NM_001815.5(CEACAM3):​c.269C>T​(p.Thr90Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEACAM3 NM_001815.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

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]

CEACAM3 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000268833 (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=0.09549436).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001815.5. 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
	CEACAM3	NM_001815.5	MANE Select	c.269C>T	p.Thr90Ile	missense	Exon 2 of 7	NP_001806.2	P40198-1
	CEACAM3	NM_001277163.3		c.269C>T	p.Thr90Ile	missense	Exon 2 of 6	NP_001264092.1	P40198-3
	CEACAM3	NR_102333.3		n.360C>T		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM3	ENST00000357396.8	TSL:1 MANE Select	c.269C>T	p.Thr90Ile	missense	Exon 2 of 7	ENSP00000349971.3	P40198-1
	CEACAM3	ENST00000344550.4	TSL:1	c.269C>T	p.Thr90Ile	missense	Exon 2 of 6	ENSP00000341725.4	P40198-3
	CEACAM3	ENST00000415495.5	TSL:1	n.269C>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000411641.1	P40198-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461170 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726948

African (AFR) AF: 0.00 AC: 0 AN: 32810

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60376

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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0060
DANN	Benign	0.27
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.012	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.5
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.082
Sift	Benign	0.77	T
Sift4G	Benign	0.65	T
Polyphen		0.22	B
Vest4		0.25
MutPred		0.48		Loss of glycosylation at T90 (P = 0.0171)
MVP		0.18
MPC		0.37
ClinPred		0.23	T
GERP RS		-6.6
Varity_R		0.080
gMVP		0.30
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr19-42301725; COSMIC: COSV105026774;