chr19-44703663-G-C

Variant names:

• chr19-44703663-G-C
• rs183860695
• NM_001039213.4:c.352G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001039213.4(CEACAM16):​c.352G>C​(p.Glu118Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,450 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E118K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CEACAM16 NM_001039213.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.81
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	NM_001039213.4	MANE Select	c.352G>C	p.Glu118Gln	missense	Exon 3 of 7	NP_001034302.2	Q2WEN9
	CEACAM16-AS1	NR_186815.1		n.348-4486C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	ENST00000587331.7	TSL:1 MANE Select	c.352G>C	p.Glu118Gln	missense	Exon 3 of 7	ENSP00000466561.1	Q2WEN9
	CEACAM16	ENST00000405314.2	TSL:5	c.352G>C	p.Glu118Gln	missense	Exon 2 of 6	ENSP00000385576.1	Q2WEN9
	CEACAM16-AS1	ENST00000590796.1	TSL:5	n.315-4486C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424450 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 703436

African (AFR) AF: 0.00 AC: 0 AN: 32888

American (AMR) AF: 0.00 AC: 0 AN: 41934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24208

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38744

South Asian (SAS) AF: 0.00 AC: 0 AN: 80978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090160

Other (OTH) AF: 0.00 AC: 0 AN: 58832

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Uncertain	0.022	D
Sift4G	Benign	0.064	T
Vest4		0.40
MVP		0.78
MPC		0.58
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.16
gMVP		0.44
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: 2

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

Other links and lift over

dbSNP: rs183860695; hg19: chr19-45206933;