19-44676294-A-C

Variant names:

• chr19-44676294-A-C
• rs1348835801
• NM_001127893.3:c.448A>C

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.448A>C​(p.Thr150Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T150S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CEACAM19 NM_001127893.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• 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=0.094488084).

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.448A>C	p.Thr150Pro	missense	Exon 3 of 8	NP_001121365.1	Q7Z692-3
	CEACAM19	NM_020219.5		c.448A>C	p.Thr150Pro	missense	Exon 3 of 8	NP_064604.2
	CEACAM19	NM_001389722.1		c.448A>C	p.Thr150Pro	missense	Exon 4 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.448A>C	p.Thr150Pro	missense	Exon 3 of 8	ENSP00000351627.4	Q7Z692-3
	CEACAM19	ENST00000403660.3	TSL:1	c.448A>C	p.Thr150Pro	missense	Exon 3 of 8	ENSP00000384887.3	Q7Z692-1
	CEACAM19	ENST00000911248.1		c.448A>C	p.Thr150Pro	missense	Exon 4 of 10	ENSP00000581307.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.1
DANN	Benign	0.86
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.030
Sift	Benign	0.21	T
Sift4G	Benign	0.077	T
Polyphen		0.70	P
Vest4		0.30
MutPred		0.36		Gain of sheet (P = 0.0266)
MVP		0.18
MPC		0.44
ClinPred		0.14	T
GERP RS		-2.7
Varity_R		0.076
gMVP		0.35
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1348835801; hg19: chr19-45179566;