ENST00000513201.1:n.175+52606A>G

Variant names:

• chr4-182196767-A-G
• rs13115107
• ENST00000513201.1:n.175+52606A>G

Variant summary

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

The ENST00000513201.1(TENM3):​n.175+52606A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,180 control chromosomes in the GnomAD database, including 4,153 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 0.21 (4153 hom., cov: 33)
• Consequence: TENM3 ENST00000513201.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 6 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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001415969.1	c.-76+52606A>G		intron_variant	Intron 1 of 28		NP_001402898.1
TENM3	NM_001415970.1	c.-76+52013A>G		intron_variant	Intron 1 of 28		NP_001402899.1
TENM3	NM_001415968.1	c.-76+52013A>G		intron_variant	Intron 1 of 28		NP_001402897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000513201.1	n.175+52606A>G		intron_variant	Intron 1 of 3	1
TENM3	ENST00000512480.5	c.-76+52013A>G		intron_variant	Intron 1 of 2	3		ENSP00000421320.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32138 AN: 152062 Hom.: 4152 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.211 AC: 32136 AN: 152180 Hom.: 4153 Cov.: 33 AF XY: 0.205 AC XY: 15253 AN XY: 74406

African (AFR) AF: 0.107 AC: 4461 AN: 41546

American (AMR) AF: 0.200 AC: 3054 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3472

East Asian (EAS) AF: 0.00811 AC: 42 AN: 5176

South Asian (SAS) AF: 0.125 AC: 605 AN: 4822

European-Finnish (FIN) AF: 0.211 AC: 2237 AN: 10586

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19936 AN: 67966

Other (OTH) AF: 0.221 AC: 468 AN: 2114

Alfa AF: 0.262 Hom.: 8668

Bravo AF: 0.203

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		2.3

Splicing

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

Other links and lift over

dbSNP: rs13115107; hg19: chr4-183117920;