NM_001127893.3:c.138C>A

Variant names:

• chr19-44672678-C-A
• rs45605232
• NM_001127893.3:c.138C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127893.3(CEACAM19):​c.138C>A​(p.Asn46Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CEACAM19 NM_001127893.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• Publications: 0 publications found

Genes affected

CEACAM19 (HGNC:31951): (CEA cell adhesion molecule 19) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23311755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127893.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM19	NM_001127893.3	MANE Select	c.138C>A	p.Asn46Lys	missense	Exon 2 of 8	NP_001121365.1	Q7Z692-3
	CEACAM19	NM_020219.5		c.138C>A	p.Asn46Lys	missense	Exon 2 of 8	NP_064604.2
	CEACAM19	NM_001389722.1		c.138C>A	p.Asn46Lys	missense	Exon 3 of 9	NP_001376651.1	Q7Z692-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM19	ENST00000358777.10	TSL:1 MANE Select	c.138C>A	p.Asn46Lys	missense	Exon 2 of 8	ENSP00000351627.4	Q7Z692-3
	CEACAM19	ENST00000403660.3	TSL:1	c.138C>A	p.Asn46Lys	missense	Exon 2 of 8	ENSP00000384887.3	Q7Z692-1
	CEACAM19	ENST00000911248.1		c.138C>A	p.Asn46Lys	missense	Exon 3 of 10	ENSP00000581307.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399332 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 691702

African (AFR) AF: 0.00 AC: 0 AN: 31104

American (AMR) AF: 0.00 AC: 0 AN: 35484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23142

East Asian (EAS) AF: 0.00 AC: 0 AN: 37136

South Asian (SAS) AF: 0.00 AC: 0 AN: 76972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5510

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1080234

Other (OTH) AF: 0.00 AC: 0 AN: 57608

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.70
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.14
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.015	D
Polyphen		0.61	P
Vest4		0.46
MutPred		0.51		Loss of sheet (P = 0.0054)
MVP		0.71
MPC		0.50
ClinPred		0.88	D
GERP RS		1.7
Varity_R		0.21
gMVP		0.16
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs45605232; hg19: chr19-45175950;