NM_001039213.4:c.505G>A

Variant names:

• chr19-44704140-G-A
• rs876661405
• NM_001039213.4:c.505G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001039213.4(CEACAM16):​c.505G>A​(p.Gly169Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEACAM16 NM_001039213.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.175

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 19-44704140-G-A is Pathogenic according to our data. Variant chr19-44704140-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 235136.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM16	NM_001039213.4	c.505G>A	p.Gly169Arg	missense_variant	Exon 4 of 7	ENST00000587331.7	NP_001034302.2
CEACAM16	XM_017026795.2	c.505G>A	p.Gly169Arg	missense_variant	Exon 3 of 5		XP_016882284.1
CEACAM16-AS1	NR_186815.1	n.348-4963C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM16	ENST00000587331.7	c.505G>A	p.Gly169Arg	missense_variant	Exon 4 of 7	1	NM_001039213.4	ENSP00000466561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 4B Pathogenic:1

Apr 30, 2019

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0080	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.14	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.8	.;N
REVEL	Uncertain	0.61
Sift	Uncertain	0.0060	.;D
Sift4G	Benign	0.41	T;T
Vest4		0.13
MVP		0.27
MPC		0.29
ClinPred		0.51	D
GERP RS		0.41
Varity_R		0.36
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.51		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.51		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs876661405; hg19: chr19-45207410;