chr19-44676417-C-T

Variant names:

• chr19-44676417-C-T
• rs1973951710
• NM_001127893.3:c.571C>T

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.571C>T​(p.His191Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: CEACAM19 NM_001127893.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.555
• 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=0.1051082).

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.571C>T	p.His191Tyr	missense	Exon 3 of 8	NP_001121365.1	Q7Z692-3
	CEACAM19	NM_020219.5		c.571C>T	p.His191Tyr	missense	Exon 3 of 8	NP_064604.2
	CEACAM19	NM_001389722.1		c.571C>T	p.His191Tyr	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.571C>T	p.His191Tyr	missense	Exon 3 of 8	ENSP00000351627.4	Q7Z692-3
	CEACAM19	ENST00000403660.3	TSL:1	c.571C>T	p.His191Tyr	missense	Exon 3 of 8	ENSP00000384887.3	Q7Z692-1
	CEACAM19	ENST00000911248.1		c.571C>T	p.His191Tyr	missense	Exon 4 of 10	ENSP00000581307.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111992

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.094
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.56
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.063
Sift	Benign	0.032	D
Sift4G	Uncertain	0.047	D
Polyphen		0.98	D
Vest4		0.25
MutPred		0.35		Loss of disorder (P = 0.046)
MVP		0.27
MPC		0.13
ClinPred		0.16	T
GERP RS		1.2
Varity_R		0.10
gMVP		0.15
Mutation Taster		=98/2	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: rs1973951710; hg19: chr19-45179689;