NM_002483.7:c.425C>A

Variant summary

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

The NM_002483.7(CEACAM6):​c.425C>A​(p.Pro142Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P142L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CEACAM6
NM_002483.7 missense, splice_region

Scores

1
15
Splicing: ADA: 0.0001399
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27
Variant links:
Genes affected
CEACAM6 (HGNC:1818): (CEA cell adhesion molecule 6) This gene encodes a protein that belongs to the carcinoembryonic antigen (CEA) family whose members are glycosyl phosphatidyl inositol (GPI) anchored cell surface glycoproteins. Members of this family play a role in cell adhesion and are widely used as tumor markers in serum immunoassay determinations of carcinoma. This gene affects the sensitivity of tumor cells to adenovirus infection. The protein encoded by this gene acts as a receptor for adherent-invasive E. coli adhesion to the surface of ileal epithelial cells in patients with Crohn's disease. This gene is clustered with genes and pseudogenes of the cell adhesion molecules subgroup of the CEA family on chromosome 19. [provided by RefSeq, Apr 2014]

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=0.0501934).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEACAM6NM_002483.7 linkc.425C>A p.Pro142Gln missense_variant, splice_region_variant Exon 3 of 6 ENST00000199764.7 NP_002474.4 P40199
CEACAM6XM_011526990.3 linkc.425C>A p.Pro142Gln missense_variant, splice_region_variant Exon 3 of 5 XP_011525292.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEACAM6ENST00000199764.7 linkc.425C>A p.Pro142Gln missense_variant, splice_region_variant Exon 3 of 6 1 NM_002483.7 ENSP00000199764.6 P40199
ENSG00000268833ENST00000601409.1 linkn.384-3168G>T intron_variant Intron 1 of 1 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.84
DANN
Benign
0.59
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.014
N
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-0.97
T
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-3.4
.;D
REVEL
Benign
0.019
Sift
Benign
0.42
.;T
Sift4G
Benign
0.70
T;T
Vest4
0.33
MutPred
0.31
Loss of glycosylation at P142 (P = 0.0907);Loss of glycosylation at P142 (P = 0.0907);
MVP
0.061
MPC
0.15
ClinPred
0.084
T
GERP RS
-0.50
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00014
dbscSNV1_RF
Benign
0.0040
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: chr19-42265157; API