rs979461820

Positions:

• chr19-44703670-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001039213.4(CEACAM16):​c.359G>C​(p.Gly120Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,411,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CEACAM16 NM_001039213.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.041098535).
• BP6: Variant 19-44703670-G-C is Benign according to our data. Variant chr19-44703670-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 505181.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM16	NM_001039213.4	c.359G>C	p.Gly120Ala	missense_variant	3/7	ENST00000587331.7	NP_001034302.2
CEACAM16	XM_017026795.2	c.359G>C	p.Gly120Ala	missense_variant	2/5		XP_016882284.1
CEACAM16-AS1	NR_186815.1	n.348-4493C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7	c.359G>C	p.Gly120Ala	missense_variant	3/7	1	NM_001039213.4	ENSP00000466561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000104 AC: 2 AN: 192294 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 103216

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000675

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000425 AC: 6 AN: 1411834 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 695686

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000736

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000277

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 16, 2016

p.Gly120Ala in exon 3 of CEACAM16: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. O f note, 5 mammals (elephant, opossum, Tasmanian devil, wallaby, and platypus) ha ve an alanine (Ala) at this position despite high nearby amino acid conservation . In addition, computational prediction tools do not suggest a high likelihood o f impact to the protein. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.096
DEOGEN2	Benign	0.0061	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.35	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.39	.;N
REVEL	Benign	0.036
Sift	Benign	1.0	.;T
Sift4G	Benign	0.54	T;T
Vest4		0.17
MVP		0.072
MPC		0.19
ClinPred		0.023	T
GERP RS		1.6
Varity_R		0.043
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs979461820; hg19: chr19-45206940;