19-41797893-A-C

Variant names:

• chr19-41797893-A-C
• rs782216874
• NM_001815.5:c.369A>C

Variant summary

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

The NM_001815.5(CEACAM3):​c.369A>C​(p.Gln123His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000041 (0 hom.)
• Consequence: CEACAM3 NM_001815.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.10

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10281339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM3	NM_001815.5	c.369A>C	p.Gln123His	missense_variant	Exon 2 of 7	ENST00000357396.8	NP_001806.2
CEACAM3	NM_001277163.3	c.369A>C	p.Gln123His	missense_variant	Exon 2 of 6		NP_001264092.1
CEACAM3	NR_102333.3	n.460A>C		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.369A>C	p.Gln123His	missense_variant	Exon 2 of 7	1	NM_001815.5	ENSP00000349971.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461128 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726836

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.369A>C (p.Q123H) alteration is located in exon 2 (coding exon 2) of the CEACAM3 gene. This alteration results from a A to C substitution at nucleotide position 369, causing the glutamine (Q) at amino acid position 123 to be replaced by a histidine (H). 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	0.32
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.2
DANN	Benign	0.29
DEOGEN2	Benign	0.032	T;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.075	T;T;.;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N;.;N;.
REVEL	Benign	0.10
Sift	Benign	0.26	T;.;T;.
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.59	P;.;.;.
Vest4		0.15
MutPred		0.50		Gain of ubiquitination at K126 (P = 0.1375);Gain of ubiquitination at K126 (P = 0.1375);Gain of ubiquitination at K126 (P = 0.1375);.;
MVP		0.48
MPC		0.13
ClinPred		0.14	T
GERP RS		0.49
Varity_R		0.21
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs782216874; hg19: chr19-42301825;