Genetic Variant CEACAM16:p.Val324Leu (chr19-44707890-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039213.4(CEACAM16):c.970G>T(p.Val324Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,142 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. 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. V324M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CEACAM16
NM_001039213.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

0 publications found

Variant links:

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 links:

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

CEACAM16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.22599858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM16	NM_001039213.4 link	c.970G>T	p.Val324Leu	missense_variant	Exon 6 of 7	ENST00000587331.7	NP_001034302.2	Q2WEN9
CEACAM16	XM_017026795.2 link	c.970G>T	p.Val324Leu	missense_variant	Exon 5 of 5		XP_016882284.1
CEACAM16-AS1	NR_186815.1 link	n.348-8713C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7 link	c.970G>T	p.Val324Leu	missense_variant	Exon 6 of 7	1	NM_001039213.4	ENSP00000466561.1		Q2WEN9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1408142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692488

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000308

AC:

AN:

32478

American (AMR)

AF:

0.00

AC:

AN:

41316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23894

East Asian (EAS)

AF:

0.00

AC:

AN:

38358

South Asian (SAS)

AF:

0.00

AC:

AN:

81038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5352

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076402

Other (OTH)

AF:

0.00

AC:

AN:

57816

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

L;L

PhyloP100

1.4

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.80

.;N

REVEL

Benign

0.044

Sift

Benign

0.14

.;T

Sift4G

Benign

0.12

T;T

Vest4

0.44

MVP

0.49

MPC

0.17

ClinPred

0.38

GERP RS

3.7

Varity_R

0.065

gMVP

0.24

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over