4-182339448-T-G

Variant names:

• chr4-182339448-T-G
• rs10520528
• NM_001080477.4:c.233-7203T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080477.4(TENM3):​c.233-7203T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,016 control chromosomes in the GnomAD database, including 18,382 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 0.48 (18382 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 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.233-7203T>G		intron	N/A	NP_001073946.1
	TENM3	NM_001415969.1		c.233-7203T>G		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.233-7203T>G		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.233-7203T>G		intron	N/A	ENSP00000424226.1
	TENM3	ENST00000513201.1	TSL:1	n.483-7203T>G		intron	N/A
	TENM3	ENST00000512480.5	TSL:3	c.233-7203T>G		intron	N/A	ENSP00000421320.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73621 AN: 151898 Hom.: 18370 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.485 AC: 73670 AN: 152016 Hom.: 18382 Cov.: 32 AF XY: 0.485 AC XY: 36051 AN XY: 74304

African (AFR) AF: 0.569 AC: 23595 AN: 41438

American (AMR) AF: 0.608 AC: 9288 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1260 AN: 3468

East Asian (EAS) AF: 0.496 AC: 2564 AN: 5168

South Asian (SAS) AF: 0.507 AC: 2447 AN: 4826

European-Finnish (FIN) AF: 0.421 AC: 4443 AN: 10560

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

European-Non Finnish (NFE) AF: 0.421 AC: 28596 AN: 67968

Other (OTH) AF: 0.482 AC: 1019 AN: 2114

Alfa AF: 0.453 Hom.: 29389

Bravo AF: 0.503

Asia WGS AF: 0.516 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		3.4
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: rs10520528; hg19: chr4-183260601;