rs375722926

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PP3BP6BS1

The NM_001039213.4(CEACAM16):c.116T>A(p.Leu39Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L39L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

CEACAM16
NM_001039213.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.40

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.794

BP6

Variant 19-44703427-T-A is Benign according to our data. Variant chr19-44703427-T-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 504866.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00023 (35/152198) while in subpopulation AFR AF = 0.000772 (32/41452). AF 95% confidence interval is 0.000562. There are 0 homozygotes in GnomAd4. There are 20 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM16	NM_001039213.4 link	c.116T>A	p.Leu39Gln	missense_variant	Exon 3 of 7	ENST00000587331.7	NP_001034302.2	Q2WEN9
CEACAM16	XM_017026795.2 link	c.116T>A	p.Leu39Gln	missense_variant	Exon 2 of 5		XP_016882284.1
CEACAM16-AS1	NR_186815.1 link	n.348-4250A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7 link	c.116T>A	p.Leu39Gln	missense_variant	Exon 3 of 7	1	NM_001039213.4	ENSP00000466561.1		Q2WEN9

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000724

AC:

AN:

248778

AF XY:

0.0000888

show subpopulations

Gnomad AFR exome

AF:

0.000906

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461514

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.000926

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111870

Other (OTH)

AF:

0.000116

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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

AF:

0.000230

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.000772

AC:

AN:

41452

American (AMR)

AF:

0.000196

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.000241

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000661

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 30, 2018

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Leu39Gln variant in CEACAM16 has not been previously reported in individua ls with hearing loss, but has been identified in 0.08% (20/23988) of African chr omosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitut e.org/; dbSNP rs375722926). Although this variant has been seen in the general p opulation, its frequency is not high enough to rule out a pathogenic role. Compu tational prediction tools and conservation analysis do not provide strong suppor t for or against an impact to the protein. In summary, the clinical significanc e of the p.Leu39Gln variant is uncertain. ACMG/AMP criteria applied: None -

not provided

Benign:1

Jul 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.4

M;M

PhyloP100

2.4

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.5

.;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.92

MVP

0.67

MPC

0.62

ClinPred

0.48

GERP RS

5.2

Varity_R

0.68

gMVP

0.88

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over