Variant 19-44672666-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001127893.3(CEACAM19):c.126G>T(p.Gln42His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,384,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CEACAM19
NM_001127893.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.481

Variant links:

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]

CEACAM19 links:

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

CEACAM16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.036390334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CEACAM19	NM_001127893.3 linkuse as main transcript	c.126G>T	p.Gln42His	missense_variant	2/8	ENST00000358777.10	NP_001121365.1
CEACAM19	NM_020219.5 linkuse as main transcript	c.126G>T	p.Gln42His	missense_variant	2/8		NP_064604.2
CEACAM19	NM_001389722.1 linkuse as main transcript	c.126G>T	p.Gln42His	missense_variant	3/9		NP_001376651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM19	ENST00000358777.10 linkuse as main transcript	c.126G>T	p.Gln42His	missense_variant	2/8	1	NM_001127893.3	ENSP00000351627	A2	Q7Z692-3
CEACAM16-AS1	ENST00000662585.1 linkuse as main transcript	n.475+26418C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000102

AC:

AN:

195570

Hom.:

AF XY:

0.0000191

AC XY:

AN XY:

104884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000660

Gnomad SAS exome

AF:

0.0000515

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1384054

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681872

show subpopulations

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:

0.0000135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.126G>T (p.Q42H) alteration is located in exon 2 (coding exon 2) of the CEACAM19 gene. This alteration results from a G to T substitution at nucleotide position 126, causing the glutamine (Q) at amino acid position 42 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

0.15

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.7

DANN

Benign

0.89

DEOGEN2

Benign

0.0039

.;.;.;.;.;.;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.65

T;.;.;.;T;T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.036

T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.025

.;.;.;.;.;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

.;.;.;.;.;N;N

REVEL

Benign

0.077

Sift

Benign

0.34

.;.;.;.;.;T;T

Sift4G

Benign

0.41

T;T;T;T;T;T;T

Polyphen

0.0020

.;.;.;.;.;.;B

Vest4

0.16, 0.15

MutPred

0.28

Loss of methylation at K45 (P = 0.0666);Loss of methylation at K45 (P = 0.0666);Loss of methylation at K45 (P = 0.0666);Loss of methylation at K45 (P = 0.0666);Loss of methylation at K45 (P = 0.0666);Loss of methylation at K45 (P = 0.0666);Loss of methylation at K45 (P = 0.0666);

MVP

0.11

MPC

0.10

ClinPred

0.015

GERP RS

-1.2

Varity_R

0.046

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over