chr4-182681099-G-A

Variant names:

• chr4-182681099-G-A
• rs4861517
• NM_001080477.4:c.1834+362G>A

Variant summary

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

The NM_001080477.4(TENM3):​c.1834+362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,006 control chromosomes in the GnomAD database, including 7,191 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 0.29 (7191 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4	c.1834+362G>A		intron_variant	Intron 10 of 27	ENST00000511685.6	NP_001073946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6	c.1834+362G>A		intron_variant	Intron 10 of 27	5	NM_001080477.4	ENSP00000424226.1
TENM3	ENST00000502950.1	n.221+362G>A		intron_variant	Intron 2 of 14	2
TENM3	ENST00000507737.1	n.366+362G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44227 AN: 151888 Hom.: 7176 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.291 AC: 44265 AN: 152006 Hom.: 7191 Cov.: 32 AF XY: 0.296 AC XY: 21982 AN XY: 74298

African (AFR) AF: 0.296 AC: 12289 AN: 41454

American (AMR) AF: 0.368 AC: 5619 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3472

East Asian (EAS) AF: 0.696 AC: 3573 AN: 5130

South Asian (SAS) AF: 0.390 AC: 1877 AN: 4814

European-Finnish (FIN) AF: 0.244 AC: 2574 AN: 10550

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16323 AN: 67990

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.260 Hom.: 5120

Bravo AF: 0.302

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.64
PhyloP100		0.50
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: rs4861517; hg19: chr4-183602252;