4-182652431-C-T

Variant names:

• chr4-182652431-C-T
• rs2037067
• NM_001080477.4:c.989-1340C>T

Variant summary

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

The NM_001080477.4(TENM3):​c.989-1340C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,014 control chromosomes in the GnomAD database, including 13,085 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 (13085 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 2 publications found

Genes affected

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.989-1340C>T		intron_variant	Intron 5 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.989-1340C>T		intron_variant	Intron 5 of 27	5	NM_001080477.4	ENSP00000424226.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61200 AN: 151894 Hom.: 13068 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.403 AC: 61249 AN: 152014 Hom.: 13085 Cov.: 32 AF XY: 0.409 AC XY: 30362 AN XY: 74292

African (AFR) AF: 0.428 AC: 17771 AN: 41474

American (AMR) AF: 0.559 AC: 8528 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3468

East Asian (EAS) AF: 0.707 AC: 3658 AN: 5172

South Asian (SAS) AF: 0.415 AC: 1995 AN: 4802

European-Finnish (FIN) AF: 0.386 AC: 4076 AN: 10548

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22915 AN: 67972

Other (OTH) AF: 0.406 AC: 858 AN: 2114

Alfa AF: 0.351 Hom.: 5368

Bravo AF: 0.419

Asia WGS AF: 0.539 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.76
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2037067; hg19: chr4-183573584;