chr19-44672935-T-C

Variant names:

• chr19-44672935-T-C
• rs1973883943
• NM_001127893.3:c.395T>C

Variant summary

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

The NM_001127893.3(CEACAM19):​c.395T>C​(p.Met132Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,512,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CEACAM19 NM_001127893.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.395T>C	p.Met132Thr	missense	Exon 2 of 8	NP_001121365.1	Q7Z692-3
	CEACAM19	NM_020219.5		c.395T>C	p.Met132Thr	missense	Exon 2 of 8	NP_064604.2
	CEACAM19	NM_001389722.1		c.395T>C	p.Met132Thr	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.395T>C	p.Met132Thr	missense	Exon 2 of 8	ENSP00000351627.4	Q7Z692-3
	CEACAM19	ENST00000403660.3	TSL:1	c.395T>C	p.Met132Thr	missense	Exon 2 of 8	ENSP00000384887.3	Q7Z692-1
	CEACAM19	ENST00000911248.1		c.395T>C	p.Met132Thr	missense	Exon 3 of 10	ENSP00000581307.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1360716 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 666692

African (AFR) AF: 0.00 AC: 0 AN: 30346

American (AMR) AF: 0.00 AC: 0 AN: 31842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21302

East Asian (EAS) AF: 0.00 AC: 0 AN: 36302

South Asian (SAS) AF: 0.00 AC: 0 AN: 70878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5368

European-Non Finnish (NFE) AF: 9.46e-7 AC: 1 AN: 1057630

Other (OTH) AF: 0.00 AC: 0 AN: 55994

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.0
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.33
Sift	Benign	0.21	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.50
MutPred		0.44		Loss of catalytic residue at M132 (P = 0.0332)
MVP		0.75
MPC		0.49
ClinPred		0.86	D
GERP RS		3.9
Varity_R		0.13
gMVP		0.35
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1973883943; hg19: chr19-45176207; COSMIC: COSV62551800; COSMIC: COSV62551800;