rs747285667
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001039213.4(CEACAM16):c.970G>A(p.Val324Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000622 in 1,560,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
CEACAM16
NM_001039213.4 missense
NM_001039213.4 missense
Scores
5
10
Clinical Significance
Conservation
PhyloP100: 1.44
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2113623).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEACAM16 | NM_001039213.4 | c.970G>A | p.Val324Met | missense_variant | 6/7 | ENST00000587331.7 | |
CEACAM16 | XM_017026795.2 | c.970G>A | p.Val324Met | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEACAM16 | ENST00000587331.7 | c.970G>A | p.Val324Met | missense_variant | 6/7 | 1 | NM_001039213.4 | P1 | |
CEACAM16-AS1 | ENST00000662585.1 | n.382-8713C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000453 AC: 10AN: 220608Hom.: 0 AF XY: 0.0000249 AC XY: 3AN XY: 120580
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GnomAD4 exome AF: 0.0000660 AC: 93AN: 1408140Hom.: 0 Cov.: 29 AF XY: 0.0000534 AC XY: 37AN XY: 692486
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74336
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 26, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Val324Met var iant in CEACAM16 has not been previously reported in individuals with hearing lo ss. This variant has been identified in 4/45370 European chromosomes by the Exom e Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs74728566 7). The valine (Val) at position 324 is not conserved in mammals, with 1 primate (gibbon) having a methionine (Met) at this position. Additional computational p rediction tools do not provide strong support for or against an impact to the pr otein. In summary, while the clinical significance of the p.Val324Met variant is uncertain, the lack of evolutionarily conservation suggests that it is more lik ely to be benign. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 228515). This variant has not been reported in the literature in individuals affected with CEACAM16-related conditions. This variant is present in population databases (rs747285667, gnomAD 0.02%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 324 of the CEACAM16 protein (p.Val324Met). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at