4-182557403-C-T

Variant names:

• chr4-182557403-C-T
• rs925669
• NM_001080477.4:c.512-43521C>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.512-43521C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,010 control chromosomes in the GnomAD database, including 20,678 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 0.50 (20678 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.512-43521C>T		intron_variant	Intron 3 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.512-43521C>T		intron_variant	Intron 3 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000510504.1	c.86-43521C>T		intron_variant	Intron 1 of 2	3		ENSP00000426914.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76088 AN: 151892 Hom.: 20640 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.501 AC: 76182 AN: 152010 Hom.: 20678 Cov.: 32 AF XY: 0.495 AC XY: 36795 AN XY: 74288

African (AFR) AF: 0.707 AC: 29320 AN: 41484

American (AMR) AF: 0.563 AC: 8597 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1676 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1977 AN: 5158

South Asian (SAS) AF: 0.398 AC: 1923 AN: 4826

European-Finnish (FIN) AF: 0.279 AC: 2945 AN: 10554

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28116 AN: 67944

Other (OTH) AF: 0.493 AC: 1037 AN: 2104

Alfa AF: 0.432 Hom.: 6567

Bravo AF: 0.534

Asia WGS AF: 0.423 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.70
PhyloP100		0.034
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: rs925669; hg19: chr4-183478556;