rs1439283

Variant names:

• chr4-181563616-C-T
• rs1439283
• ENST00000763321.1:n.125+21668C>T

Variant summary

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

The ENST00000763321.1(ENSG00000299420):​n.125+21668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,018 control chromosomes in the GnomAD database, including 18,125 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 0.48 (18125 hom., cov: 32)
• Consequence: ENSG00000299420 ENST00000763321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	XM_017008385.2	c.-400+115844C>T		intron_variant	Intron 1 of 32		XP_016863874.1
TENM3	XM_017008389.2	c.-400+115844C>T		intron_variant	Intron 1 of 32		XP_016863878.1
TENM3	XM_017008390.2	c.-400+115844C>T		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.125+21668C>T		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72401 AN: 151900 Hom.: 18096 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.477 AC: 72489 AN: 152018 Hom.: 18125 Cov.: 32 AF XY: 0.467 AC XY: 34670 AN XY: 74298

African (AFR) AF: 0.611 AC: 25337 AN: 41474

American (AMR) AF: 0.490 AC: 7482 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1776 AN: 3472

East Asian (EAS) AF: 0.185 AC: 958 AN: 5166

South Asian (SAS) AF: 0.305 AC: 1466 AN: 4814

European-Finnish (FIN) AF: 0.309 AC: 3264 AN: 10558

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30644 AN: 67954

Other (OTH) AF: 0.466 AC: 985 AN: 2112

Alfa AF: 0.466 Hom.: 56273

Bravo AF: 0.498

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs1439283; hg19: chr4-182484769;