chr19-41579536-C-T

Variant names:

• chr19-41579536-C-T
• NM_001098506.4:c.608C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001098506.4(CEACAM21):​c.608C>T​(p.Pro203Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P203H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEACAM21 NM_001098506.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29060012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM21	NM_001098506.4	c.608C>T	p.Pro203Leu	missense_variant	Exon 3 of 7	ENST00000401445.4	NP_001091976.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM21	ENST00000401445.4	c.608C>T	p.Pro203Leu	missense_variant	Exon 3 of 7	1	NM_001098506.4	ENSP00000385739.2
CEACAM21	ENST00000457737.5	n.*115C>T		non_coding_transcript_exon_variant	Exon 3 of 7	1		ENSP00000390697.1
CEACAM21	ENST00000457737.5	n.*115C>T		3_prime_UTR_variant	Exon 3 of 7	1		ENSP00000390697.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460612 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726486

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.9
DANN	Uncertain	0.98
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.0059	N
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Pathogenic	-9.5	D;D;D
REVEL	Benign	0.047
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.021	D;T;T
Vest4		0.18
MutPred		0.48		.;Loss of disorder (P = 0.0736);Loss of disorder (P = 0.0736);
MVP		0.14
MPC		0.057
ClinPred		0.94	D
GERP RS		-1.8
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-42085889;