4-182556176-G-A

Variant names:

• chr4-182556176-G-A
• rs10013166
• NM_001080477.4:c.512-44748G>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.512-44748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,022 control chromosomes in the GnomAD database, including 12,910 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 0.39 (12910 hom., cov: 32)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• 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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	NM_001080477.4	MANE Select	c.512-44748G>A		intron	N/A	NP_001073946.1	Q9P273
	TENM3	NM_001415969.1		c.512-44748G>A		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.512-44748G>A		intron	N/A	NP_001402899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3	ENST00000511685.6	TSL:5 MANE Select	c.512-44748G>A		intron	N/A	ENSP00000424226.1	Q9P273
	TENM3	ENST00000851056.1		c.512-44748G>A		intron	N/A	ENSP00000521125.1
	TENM3	ENST00000851057.1		c.512-44748G>A		intron	N/A	ENSP00000521126.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59430 AN: 151906 Hom.: 12909 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.391 AC: 59448 AN: 152022 Hom.: 12910 Cov.: 32 AF XY: 0.395 AC XY: 29350 AN XY: 74292

African (AFR) AF: 0.206 AC: 8530 AN: 41490

American (AMR) AF: 0.365 AC: 5576 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1503 AN: 3466

East Asian (EAS) AF: 0.558 AC: 2878 AN: 5162

South Asian (SAS) AF: 0.403 AC: 1940 AN: 4810

European-Finnish (FIN) AF: 0.587 AC: 6200 AN: 10554

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31516 AN: 67950

Other (OTH) AF: 0.412 AC: 870 AN: 2114

Alfa AF: 0.440 Hom.: 61731

Bravo AF: 0.370

Asia WGS AF: 0.468 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.0
DANN	Benign	0.39
PhyloP100		1.7
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: rs10013166; hg19: chr4-183477329;