19-44676298-A-C

Position:

• chr19-44676298-A-C

Variant summary

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

The NM_001127893.3(CEACAM19):​c.452A>C​(p.His151Pro) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEACAM19 NM_001127893.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.156

Genes affected

CEACAM19 (HGNC:31951): (CEA cell adhesion molecule 19) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

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=0.08777583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM19	NM_001127893.3	c.452A>C	p.His151Pro	missense_variant	3/8	ENST00000358777.10	NP_001121365.1
CEACAM19	NM_020219.5	c.452A>C	p.His151Pro	missense_variant	3/8		NP_064604.2
CEACAM19	NM_001389722.1	c.452A>C	p.His151Pro	missense_variant	4/9		NP_001376651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM19	ENST00000358777.10	c.452A>C	p.His151Pro	missense_variant	3/8	1	NM_001127893.3	ENSP00000351627.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.452A>C (p.H151P) alteration is located in exon 3 (coding exon 3) of the CEACAM19 gene. This alteration results from a A to C substitution at nucleotide position 452, causing the histidine (H) at amino acid position 151 to be replaced by a proline (P). 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	0.074
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.8
DANN	Benign	0.81
DEOGEN2	Benign	0.013	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.011
Sift	Benign	0.16	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.072	.;B
Vest4		0.15
MutPred		0.32		Gain of glycosylation at H151 (P = 0.0186);Gain of glycosylation at H151 (P = 0.0186);
MVP		0.21
MPC		0.17
ClinPred		0.059	T
GERP RS		0.94
Varity_R		0.11
gMVP		0.27

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: chr19-45179570;