19-41579389-C-T

Variant names:

• chr19-41579389-C-T
• NM_001098506.4:c.461C>T

Variant summary

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

The NM_001098506.4(CEACAM21):​c.461C>T​(p.Thr154Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 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)
• Consequence: CEACAM21 NM_001098506.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• Publications: 0 publications found

Genes affected

CEACAM21 (HGNC:28834): (CEA cell adhesion molecule 21) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10015699).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098506.4. 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
	CEACAM21	NM_001098506.4	MANE Select	c.461C>T	p.Thr154Ile	missense	Exon 3 of 7	NP_001091976.3	Q3KPI0-1
	CEACAM21	NM_033543.6		c.461C>T	p.Thr154Ile	missense	Exon 3 of 7	NP_291021.4
	CEACAM21	NM_001288773.3		c.77C>T	p.Thr26Ile	missense	Exon 4 of 8	NP_001275702.2	A0A0B4J1W4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM21	ENST00000401445.4	TSL:1 MANE Select	c.461C>T	p.Thr154Ile	missense	Exon 3 of 7	ENSP00000385739.2	Q3KPI0-1
	CEACAM21	ENST00000187608.13	TSL:1	c.461C>T	p.Thr154Ile	missense	Exon 3 of 7	ENSP00000187608.9	Q3KPI0-2
	CEACAM21	ENST00000457737.5	TSL:1	n.544C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000390697.1	Q3KPI0-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.27
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.97
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0081	N
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.2
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.031
Sift	Benign	0.038	D
Sift4G	Benign	0.16	T
Vest4		0.054
MutPred		0.37		Loss of glycosylation at T154 (P = 0.0167)
MVP		0.040
MPC		0.17
ClinPred		0.25	T
GERP RS		1.2
PromoterAI		-0.0080	Neutral
gMVP		0.13
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

hg19: chr19-42085742;