NM_001080477.4:c.512-46143A>C

Variant names:

• chr4-182554781-A-C
• rs13144500
• NM_001080477.4:c.512-46143A>C

Variant summary

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

The NM_001080477.4(TENM3):​c.512-46143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,218 control chromosomes in the GnomAD database, including 1,408 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 0.12 (1408 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 3 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 = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.512-46143A>C		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.512-46143A>C		intron_variant	Intron 3 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000510504.1	c.86-46143A>C		intron_variant	Intron 1 of 2	3		ENSP00000426914.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18472 AN: 152100 Hom.: 1411 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.121 AC: 18466 AN: 152218 Hom.: 1408 Cov.: 32 AF XY: 0.124 AC XY: 9200 AN XY: 74408

African (AFR) AF: 0.0319 AC: 1327 AN: 41580

American (AMR) AF: 0.108 AC: 1647 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1160 AN: 5174

South Asian (SAS) AF: 0.192 AC: 926 AN: 4814

European-Finnish (FIN) AF: 0.191 AC: 2021 AN: 10572

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10471 AN: 67998

Other (OTH) AF: 0.125 AC: 265 AN: 2114

Alfa AF: 0.136 Hom.: 3029

Bravo AF: 0.112

Asia WGS AF: 0.205 AC: 709 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.50
PhyloP100		-0.066
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: rs13144500; hg19: chr4-183475934;