19-44512066-G-A

Position:

• chr19-44512066-G-A

Variant summary

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

The NM_001102597.3(CEACAM20):​c.1526C>T​(p.Pro509Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000962 in 1,455,856 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: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: CEACAM20 NM_001102597.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.186

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=0.12171847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM20	NM_001102597.3	c.1526C>T	p.Pro509Leu	missense_variant	9/12	ENST00000614924.5	NP_001096067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM20	ENST00000614924.5	c.1526C>T	p.Pro509Leu	missense_variant	9/12	1	NM_001102597.3	ENSP00000481937	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000962 AC: 14 AN: 1455856 Hom.: 0 Cov.: 31 AF XY: 0.00000691 AC XY: 5 AN XY: 723416

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: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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

May 17, 2023

The c.1526C>T (p.P509L) alteration is located in exon 9 (coding exon 9) of the CEACAM20 gene. This alteration results from a C to T substitution at nucleotide position 1526, causing the proline (P) at amino acid position 509 to be replaced by a leucine (L). 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	0.082
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.8
DANN	Benign	0.66
DEOGEN2	Benign	0.021	.;.;.;T;.;.
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.80	T;T;T;T;T;T
MetaRNN	Benign	0.12	T;T;T;T;T;T
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.091	T;D;D;T;T;T
Polyphen		0.056	.;.;.;B;.;.
Vest4		0.089
MVP		0.29
GERP RS		1.4
Varity_R		0.037
gMVP		0.30

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

Other links and lift over

dbSNP: rs1971018925; hg19: chr19-45016124;