ENST00000763321.1:n.126-39442T>A

Variant names:

• chr4-181594506-T-A
• rs1371217
• ENST00000763321.1:n.126-39442T>A

Variant summary

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

The ENST00000763321.1(ENSG00000299420):​n.126-39442T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,868 control chromosomes in the GnomAD database, including 18,195 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 0.49 (18195 hom., cov: 31)
• Consequence: ENSG00000299420 ENST00000763321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-399-144981T>A		intron_variant	Intron 1 of 32		XP_016863874.1
TENM3	XM_017008389.2	c.-399-144981T>A		intron_variant	Intron 1 of 32		XP_016863878.1
TENM3	XM_017008390.2	c.-399-144981T>A		intron_variant	Intron 1 of 31		XP_016863879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000299420	ENST00000763321.1	n.126-39442T>A		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73868 AN: 151750 Hom.: 18188 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.487 AC: 73890 AN: 151868 Hom.: 18195 Cov.: 31 AF XY: 0.484 AC XY: 35944 AN XY: 74192

African (AFR) AF: 0.456 AC: 18874 AN: 41414

American (AMR) AF: 0.494 AC: 7545 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2430 AN: 5136

South Asian (SAS) AF: 0.413 AC: 1981 AN: 4800

European-Finnish (FIN) AF: 0.470 AC: 4941 AN: 10520

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34845 AN: 67948

Other (OTH) AF: 0.456 AC: 961 AN: 2108

Alfa AF: 0.344 Hom.: 886

Bravo AF: 0.487

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs1371217; hg19: chr4-182515659;