19-44520501-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001102597.3(CEACAM20):c.1003A>G(p.Ser335Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000815 in 1,613,406 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00072 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (3 hom.)
• Consequence: CEACAM20 NM_001102597.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM20	NM_001102597.3	c.1003A>G	p.Ser335Gly	missense_variant	5/12	ENST00000614924.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM20	ENST00000614924.5	c.1003A>G	p.Ser335Gly	missense_variant	5/12	1	NM_001102597.3	A2

Frequencies

GnomAD3 genomes AF: 0.000710 AC: 108 AN: 152190 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000848 AC: 211 AN: 248756 Hom.: 3 AF XY: 0.000948 AC XY: 128 AN XY: 134988

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00856

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000808

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.000825 AC: 1206 AN: 1461098 Hom.: 3 Cov.: 31 AF XY: 0.000911 AC XY: 662 AN XY: 726826

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00869

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000835

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000754

Gnomad4 OTH exome AF: 0.000846

GnomAD4 genome AF: 0.000716 AC: 109 AN: 152308 Hom.: 1 Cov.: 32 AF XY: 0.000685 AC XY: 51 AN XY: 74480

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000972 Hom.: 0

Bravo AF: 0.000548

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000258 AC: 1

ESP6500EA AF: 0.000847 AC: 7

ExAC AF: 0.000621 AC: 75

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Aug 10, 2021

The c.1003A>G (p.S335G) alteration is located in exon 5 (coding exon 5) of the CEACAM20 gene. This alteration results from a A to G substitution at nucleotide position 1003, causing the serine (S) at amino acid position 335 to be replaced by a glycine (G). 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	0.32
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.11
Cadd	Benign	18
Dann	Benign	0.52
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.75	T;T;T;T;T;T
MetaRNN	Benign	0.0095	T;T;T;T;T;T
PrimateAI	Benign	0.47	T
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		1.0	.;.;.;D;.;.
Vest4		0.37
MVP		0.29
GERP RS		4.3
Varity_R		0.14
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200961907; hg19: chr19-45024535;