chr19-44672625-G-A

Position:

• chr19-44672625-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001127893.3(CEACAM19):​c.85G>A​(p.Gly29Ser) 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: 32)
• Consequence: CEACAM19 NM_001127893.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.224

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05709958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM19	NM_001127893.3	c.85G>A	p.Gly29Ser	missense_variant	2/8	ENST00000358777.10	NP_001121365.1
CEACAM19	NM_020219.5	c.85G>A	p.Gly29Ser	missense_variant	2/8		NP_064604.2
CEACAM19	NM_001389722.1	c.85G>A	p.Gly29Ser	missense_variant	3/9		NP_001376651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM19	ENST00000358777.10	c.85G>A	p.Gly29Ser	missense_variant	2/8	1	NM_001127893.3	ENSP00000351627.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 20, 2024

The c.85G>A (p.G29S) alteration is located in exon 2 (coding exon 2) of the CEACAM19 gene. This alteration results from a G to A substitution at nucleotide position 85, causing the glycine (G) at amino acid position 29 to be replaced by a serine (S). 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	0.089
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.8
DANN	Benign	0.77
DEOGEN2	Benign	0.0063	.;.;.;.;.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.75	T;.;.;.;T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.057	T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	.;.;.;.;.;L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	.;.;.;.;.;N;N
REVEL	Benign	0.040
Sift	Benign	0.22	.;.;.;.;.;T;T
Sift4G	Benign	0.13	T;T;T;T;T;T;T
Polyphen		0.011	.;.;.;.;.;.;B
Vest4		0.22, 0.21
MutPred		0.40		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.41
MPC		0.10
ClinPred		0.027	T
GERP RS		-3.9
Varity_R		0.047
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-45175897;