19-41577292-C-T

Variant names:

• chr19-41577292-C-T
• rs782014553
• NM_001098506.4:c.157C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001098506.4(CEACAM21):​c.157C>T​(p.Leu53Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 11/19 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. L53I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CEACAM21 NM_001098506.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

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.157C>T	p.Leu53Phe	missense	Exon 2 of 7	NP_001091976.3	Q3KPI0-1
	CEACAM21	NM_033543.6		c.157C>T	p.Leu53Phe	missense	Exon 2 of 7	NP_291021.4
	CEACAM21	NM_001288773.3		c.-311C>T		5_prime_UTR	Exon 3 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.157C>T	p.Leu53Phe	missense	Exon 2 of 7	ENSP00000385739.2	Q3KPI0-1
	CEACAM21	ENST00000187608.13	TSL:1	c.157C>T	p.Leu53Phe	missense	Exon 2 of 7	ENSP00000187608.9	Q3KPI0-2
	CEACAM21	ENST00000457737.5	TSL:1	n.157C>T		non_coding_transcript_exon	Exon 2 of 7	ENSP00000390697.1	Q3KPI0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461838 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

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

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111968

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.4
DANN	Uncertain	1.0
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.0098	N
M_CAP	Benign	0.0011	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.1	T
PhyloP100		-0.25
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.016	D
Vest4		0.21
MutPred		0.89		Gain of glycosylation at S54 (P = 0.1308)
MVP		0.14
MPC		0.31
ClinPred		0.90	D
GERP RS		-3.2
gMVP		0.24
Mutation Taster		=298/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs782014553; hg19: chr19-42083644;