NM_001080477.4:c.5305-1250G>T

Variant names:

• chr4-182787843-G-T
• rs10006225
• NM_001080477.4:c.5305-1250G>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.5305-1250G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 149,940 control chromosomes in the GnomAD database, including 1,389 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 0.075 (1389 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080477.4. 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
	TENM3	NM_001080477.4	MANE Select	c.5305-1250G>T		intron	N/A	NP_001073946.1
	TENM3	NM_001415969.1		c.5326-1250G>T		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.5326-1250G>T		intron	N/A	NP_001402899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.5305-1250G>T		intron	N/A	ENSP00000424226.1

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 11184 AN: 149848 Hom.: 1383 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000423

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0163

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0748 AC: 11219 AN: 149940 Hom.: 1389 Cov.: 32 AF XY: 0.0725 AC XY: 5286 AN XY: 72886

African (AFR) AF: 0.256 AC: 10493 AN: 40942

American (AMR) AF: 0.0358 AC: 537 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5038

South Asian (SAS) AF: 0.000424 AC: 2 AN: 4712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9782

Middle Eastern (MID) AF: 0.0175 AC: 5 AN: 286

European-Non Finnish (NFE) AF: 0.000989 AC: 67 AN: 67732

Other (OTH) AF: 0.0549 AC: 114 AN: 2076

Alfa AF: 0.0253 Hom.: 630

Bravo AF: 0.0847

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.9
DANN	Benign	0.78
PhyloP100		1.1
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: rs10006225; hg19: chr4-183708996;