Genetic Variant CEACAM16:p.Ala170Pro (chr19-44704143-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001039213.4(CEACAM16):c.508G>C(p.Ala170Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,441,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A170T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CEACAM16
NM_001039213.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.281

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0594199).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039213.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	NM_001039213.4	MANE Select	c.508G>C	p.Ala170Pro	missense	Exon 4 of 7	NP_001034302.2
	CEACAM16-AS1	NR_186815.1		n.348-4966C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEACAM16	ENST00000587331.7	TSL:1 MANE Select	c.508G>C	p.Ala170Pro	missense	Exon 4 of 7	ENSP00000466561.1
CEACAM16	ENST00000405314.2	TSL:5	c.508G>C	p.Ala170Pro	missense	Exon 3 of 6	ENSP00000385576.1
CEACAM16-AS1	ENST00000590796.1	TSL:5	n.315-4966C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000143

AC:

AN:

210060

AF XY:

0.00000871

show subpopulations

Gnomad AFR exome

AF:

0.0000875

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000534

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1441118

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

715416

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32862

American (AMR)

AF:

0.00

AC:

AN:

42196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25740

East Asian (EAS)

AF:

0.00

AC:

AN:

38164

South Asian (SAS)

AF:

0.00

AC:

AN:

83170

European-Finnish (FIN)

AF:

0.0000196

AC:

AN:

50892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5222

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103394

Other (OTH)

AF:

0.0000168

AC:

AN:

59478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.4

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.047

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.59

M_CAP

Benign

0.0073

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

PhyloP100

-0.28

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.9

REVEL

Benign

0.036

Sift

Benign

0.039

Sift4G

Benign

0.12

Vest4

0.20

MVP

0.061

MPC

0.18

ClinPred

0.021

GERP RS

-3.3

Varity_R

0.27

gMVP

0.43

Mutation Taster

=75/25

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over