rs4862046

Variant names:

• chr4-182379461-A-G
• rs4862046
• NM_001080477.4:c.511+32532A>G

Variant summary

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

The NM_001415969.1(TENM3):​c.511+32532A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,194 control chromosomes in the GnomAD database, including 60,123 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 0.89 (60123 hom., cov: 32)
• Consequence: TENM3 NM_001415969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• 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: 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001415969.1. 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.511+32532A>G		intron	N/A	NP_001073946.1
	TENM3	NM_001415969.1		c.511+32532A>G		intron	N/A	NP_001402898.1
	TENM3	NM_001415970.1		c.511+32532A>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.511+32532A>G		intron	N/A	ENSP00000424226.1
	TENM3	ENST00000851056.1		c.511+32532A>G		intron	N/A	ENSP00000521125.1
	TENM3	ENST00000851057.1		c.511+32532A>G		intron	N/A	ENSP00000521126.1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134759 AN: 152076 Hom.: 60085 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.876

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

GnomAD4 genome AF: 0.886 AC: 134846 AN: 152194 Hom.: 60123 Cov.: 32 AF XY: 0.881 AC XY: 65574 AN XY: 74406

African (AFR) AF: 0.910 AC: 37782 AN: 41498

American (AMR) AF: 0.840 AC: 12856 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3103 AN: 3472

East Asian (EAS) AF: 0.582 AC: 3003 AN: 5162

South Asian (SAS) AF: 0.854 AC: 4115 AN: 4818

European-Finnish (FIN) AF: 0.876 AC: 9288 AN: 10602

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61713 AN: 68024

Other (OTH) AF: 0.870 AC: 1835 AN: 2110

Alfa AF: 0.890 Hom.: 35211

Bravo AF: 0.883

Asia WGS AF: 0.700 AC: 2435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.63
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: rs4862046; hg19: chr4-183300614;