rs387907149

Positions:

• chr19-44704053-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001039213.4(CEACAM16):​c.418A>C​(p.Thr140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEACAM16 NM_001039213.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.29

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-44704053-A-C is Pathogenic according to our data. Variant chr19-44704053-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 31238.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM16	NM_001039213.4	c.418A>C	p.Thr140Pro	missense_variant	4/7	ENST00000587331.7	NP_001034302.2
CEACAM16	XM_017026795.2	c.418A>C	p.Thr140Pro	missense_variant	3/5		XP_016882284.1
CEACAM16-AS1	NR_186815.1	n.348-4876T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7	c.418A>C	p.Thr140Pro	missense_variant	4/7	1	NM_001039213.4	ENSP00000466561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 4B Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 08, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.61	.;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	.;D
REVEL	Benign	0.27
Sift	Benign	0.063	.;T
Sift4G	Uncertain	0.014	D;D
Vest4		0.54
MVP		0.54
MPC		0.67
ClinPred		0.89	D
GERP RS		2.0
Varity_R		0.53
gMVP		0.70

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

LitVar

Other links and lift over

dbSNP: rs387907149; hg19: chr19-45207323;