NM_001039213.4:c.941-14C>A

Variant names:

• chr19-44707847-C-A
• rs10426475
• NM_001039213.4:c.941-14C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001039213.4(CEACAM16):​c.941-14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,362,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CEACAM16 NM_001039213.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.941-14C>A		intron	N/A	NP_001034302.2
	CEACAM16-AS1	NR_186815.1		n.348-8670G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	ENST00000587331.7	TSL:1 MANE Select	c.941-14C>A		intron	N/A	ENSP00000466561.1
	CEACAM16	ENST00000405314.2	TSL:5	c.941-14C>A		intron	N/A	ENSP00000385576.1
	CEACAM16-AS1	ENST00000590796.1	TSL:5	n.314+8103G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1362628 Hom.: 0 Cov.: 29 AF XY: 0.00000150 AC XY: 1 AN XY: 665102

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31276

American (AMR) AF: 0.00 AC: 0 AN: 35302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21038

East Asian (EAS) AF: 0.00 AC: 0 AN: 37450

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1057208

Other (OTH) AF: 0.00 AC: 0 AN: 56054

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	22
DANN	Benign	0.41
PhyloP100		-0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.77		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.77		Position offset: 2

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

Other links and lift over

dbSNP: rs10426475; hg19: chr19-45211119;