Genetic Variant CEACAM21:p.Ala209Thr (chr19-41579553-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098506.4(CEACAM21):c.625G>A(p.Ala209Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,455,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CEACAM21
NM_001098506.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.213

Variant links:

Genes affected

CEACAM21 (HGNC:28834): (CEA cell adhesion molecule 21) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEACAM21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.20613915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM21	NM_001098506.4 link	c.625G>A	p.Ala209Thr	missense_variant	Exon 3 of 7	ENST00000401445.4	NP_001091976.3	Q3KPI0-1A0A0G2JSC8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEACAM21	ENST00000401445.4 link	c.625G>A	p.Ala209Thr	missense_variant	Exon 3 of 7	1	NM_001098506.4	ENSP00000385739.2	Q3KPI0-1
CEACAM21	ENST00000457737.5 link	n.*132G>A		non_coding_transcript_exon_variant	Exon 3 of 7	1		ENSP00000390697.1	Q3KPI0-3
CEACAM21	ENST00000457737.5 link	n.*132G>A		3_prime_UTR_variant	Exon 3 of 7	1		ENSP00000390697.1	Q3KPI0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000253

AC:

AN:

236716

Hom.:

AF XY:

0.0000312

AC XY:

AN XY:

128228

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000234

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1455314

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.625G>A (p.A209T) alteration is located in exon 3 (coding exon 3) of the CEACAM21 gene. This alteration results from a G to A substitution at nucleotide position 625, causing the alanine (A) at amino acid position 209 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.3

DANN

Benign

0.16

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.0076

M_CAP

Benign

0.0041

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Uncertain

-3.0

D;N;N

REVEL

Benign

0.068

Sift

Benign

0.048

D;T;T

Sift4G

Benign

0.17

T;T;T

Vest4

0.065

MutPred

0.48

.;Gain of phosphorylation at A209 (P = 0.0736);Gain of phosphorylation at A209 (P = 0.0736);

MVP

0.20

MPC

0.13

ClinPred

0.60

GERP RS

1.4

gMVP

0.13

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