19-44524010-C-T

Variant summary

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

The NM_001102597.3(CEACAM20):c.448G>A(p.Asp150Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,400,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 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: 0.000010 (0 hom.)
• Consequence: CEACAM20 NM_001102597.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.185

Genes affected

CEACAM20 (HGNC:24879): (CEA cell adhesion molecule 20) Predicted to be involved in positive regulation of cytokine production. Predicted to act upstream of or within response to bacterium. Predicted to be located in apical plasma membrane and microvillus membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08029798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM20	NM_001102597.3	c.448G>A	p.Asp150Asn	missense_variant	3/12	ENST00000614924.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM20	ENST00000614924.5	c.448G>A	p.Asp150Asn	missense_variant	3/12	1	NM_001102597.3	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000625 AC: 1 AN: 159894 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 84128

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000893

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: 0.0000100 AC: 14 AN: 1400324 Hom.: 0 Cov.: 31 AF XY: 0.00000869 AC XY: 6 AN XY: 690760

Gnomad4 AFR exome AF: 0.0000628

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000741

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

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

Sep 13, 2023

The c.448G>A (p.D150N) alteration is located in exon 3 (coding exon 3) of the CEACAM20 gene. This alteration results from a G to A substitution at nucleotide position 448, causing the aspartic acid (D) at amino acid position 150 to be replaced by an asparagine (N). 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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	4.7
Dann	Benign	0.59
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.69	T;T;T;T;T;T
MetaRNN	Benign	0.080	T;T;T;T;T;T
PrimateAI	Benign	0.43	T
Sift4G	Benign	0.43	T;T;T;T;T;T
Polyphen		1.0	.;.;.;D;.;.
Vest4		0.094
MVP		0.21
GERP RS		-2.7
Varity_R		0.036
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs372020630; hg19: chr19-45028043;