ENST00000763321.1:n.410-32703A>G

Variant names:

• chr4-181783398-A-G
• rs6855088
• ENST00000763321.1:n.410-32703A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000763321.1(ENSG00000299420):​n.410-32703A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,960 control chromosomes in the GnomAD database, including 2,555 homozygotes. 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: 𝑓 0.18 (2555 hom., cov: 32)
• Consequence: ENSG00000299420 ENST00000763321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 7 publications found

Genes affected

ENSG00000299420 (HGNC:):

TENM3 (HGNC:29944): (teneurin transmembrane protein 3) This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

TENM3 Gene-Disease associations (from GenCC):

• microphthalmia, isolated, with coloboma 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000763321.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000299420	ENST00000763321.1		n.410-32703A>G		intron	N/A
	ENSG00000299420	ENST00000763322.1		n.164+43749A>G		intron	N/A
	ENSG00000299420	ENST00000763323.1		n.164+43749A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27396 AN: 151844 Hom.: 2548 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.180 AC: 27416 AN: 151960 Hom.: 2555 Cov.: 32 AF XY: 0.183 AC XY: 13617 AN XY: 74266

African (AFR) AF: 0.152 AC: 6295 AN: 41472

American (AMR) AF: 0.223 AC: 3393 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1274 AN: 5136

South Asian (SAS) AF: 0.181 AC: 875 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2284 AN: 10538

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11921 AN: 67968

Other (OTH) AF: 0.181 AC: 382 AN: 2114

Alfa AF: 0.176 Hom.: 10903

Bravo AF: 0.182

Asia WGS AF: 0.242 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.077
DANN	Benign	0.50
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs6855088; hg19: chr4-182704551;