ENST00000509012.5:n.378+45596C>A

Variant names:

• chr4-181967066-G-T
• rs9992244
• ENST00000509012.5:n.378+45596C>A

Variant summary

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

The ENST00000509012.5(TENM3-AS1):​n.378+45596C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,708 control chromosomes in the GnomAD database, including 12,477 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 0.40 (12477 hom., cov: 32)
• Consequence: TENM3-AS1 ENST00000509012.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 3 publications found

Genes affected

TENM3-AS1 (HGNC:28076): (TENM3 antisense RNA 1)

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509012.5. 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
	TENM3-AS1	ENST00000509012.5	TSL:4	n.378+45596C>A		intron	N/A
	ENSG00000299420	ENST00000763322.1		n.246-74598G>T		intron	N/A
	ENSG00000299420	ENST00000763323.1		n.246-74598G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60012 AN: 151590 Hom.: 12449 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.396 AC: 60093 AN: 151708 Hom.: 12477 Cov.: 32 AF XY: 0.392 AC XY: 29053 AN XY: 74096

African (AFR) AF: 0.510 AC: 21094 AN: 41348

American (AMR) AF: 0.286 AC: 4346 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1473 AN: 5146

South Asian (SAS) AF: 0.298 AC: 1433 AN: 4802

European-Finnish (FIN) AF: 0.397 AC: 4161 AN: 10468

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25375 AN: 67940

Other (OTH) AF: 0.390 AC: 822 AN: 2110

Alfa AF: 0.379 Hom.: 30427

Bravo AF: 0.394

Asia WGS AF: 0.338 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.46
PhyloP100		-0.73

Splicing

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

Other links and lift over

dbSNP: rs9992244; hg19: chr4-182888219;